詳細

細見　光一 （ホソミ　コウイチ）

  • 薬学部 医療薬学科　教授
Last Updated :2024/04/25

コミュニケーション情報 byコメンテータガイド

  • コメント

    医薬品適正使用の推進に向けて、医療ビッグデータを扱い、副作用やポリファーマシーのデータ解析を研究しています。データサイエンスのノウハウをドラッグリポジショニング研究にも展開しています。

研究者情報

学位

  • 博士（薬学）

ホームページURL

J-Global ID

現在の研究分野（キーワード）

    医薬品適正使用の推進に向けて、医療ビッグデータを扱い、副作用やポリファーマシーのデータ解析を研究しています。データサイエンスのノウハウをドラッグリポジショニング研究にも展開しています。

研究分野

  • ライフサイエンス / 医療薬学

研究活動情報

論文

  • Y Tanaka; R Ota; A Hirata; S Yokoyama; C Nakagawa; T Uno; K Hosomi
    Die Pharmazie 78 11 238 - 244 2023年12月 
    In patients with type 2 diabetes mellitus (T2DM), controlling serum uric acid (SUA) and blood glucose levels is important. Moreover, sodium-glucose cotransporter 2 (SGLT2) inhibitors decrease SUA levels by accelerating urinary uric acid excretion. We investigated the effect of baseline urinary glucose levels on the relationship between SGLT2 inhibitors and SUA levels. We conducted a retrospective observational study using the electronic medical records of patients with T2DM of Kindai University Nara Hospital (April 2013 to March 2022). We divided the patients into two groups according to their baseline urinary glucose levels: the N-UG group, which included patients with negative urinary glucose strip test results (-), and the P-UG group, which included patients with positive urinary glucose strip test results (± or more). The changes in SUA levels before and after SGLT2 inhibitor administration were investigated. For comparison, the changes in SUA levels before and after the prescription of antidiabetic agents, excluding SGLT2 inhibitors, were also investigated. Our results revealed that SGLT2 inhibitors significantly decreased the SUA levels in patients in the N-UG group but tended to decrease its levels in those in the P-UG group. Regardless of the urinary glucose status at baseline, the administration of SGLT2 inhibitors may be useful for patients with T2DM to prevent the complications of hyperuricemia.
  • Yuki Tanaka; Satoshi Yokoyama; Chihiro Nakagawa; Takaya Uno; Kouichi Hosomi
    International journal of clinical pharmacology and therapeutics 61 11 492 - 502 2023年11月 
    OBJECTIVE: Pancreatic cancer-related mortality is increasing worldwide, and prevention methods and effective novel therapies are required. In pancreatic cancer, sodium-glucose cotransporters (SGLT) are involved in glucose uptake. This study aimed to clarify the association between SGLT2 inhibitors and pancreatic cancer development. MATERIALS AND METHODS: A nested case-control study was conducted using the JMDC administrative claims database (January 2005 to June 2020). Patients newly diagnosed with type 2 diabetes mellitus (T2DM) were included, and cases were defined as patients who developed pancreatic cancer. Patients with outcomes were randomly matched to a maximum of 20 controls according to age (± 5 years), sex, and calendar date (month and year) of the first T2DM diagnosis through risk set sampling. RESULTS: Of the 181,107 T2DM patients, 363 cases and 7,043 controls were selected with 14 and 457 patients prescribed SGLT2 inhibitors, respectively. Cumulative administration of SGLT2 inhibitors for > 180 days was significantly inversely associated with the development of pancreatic cancer (adjusted odds ratio: 0.58, 95% confidence interval: 0.31 - 0.99). CONCLUSION: SGLT2 inhibitors may reduce the risk of developing pancreatic cancer in T2DM patients. The number of patients over 65 years of age was small in this study due to the nature of the data source. Further studies with larger sample sizes including older patients are needed.
  • Satoshi Yokoyama; Chihiro Nakagawa; Kouichi Hosomi
    Scientific reports 13 1 11677 - 11677 2023年07月 
    The association between statins and open-angle glaucoma (OAG) remains controversial. This study investigated the relationship between statins and OAG in Japanese patients with dyslipidemia using the Japanese administrative claims database. A nested case-control study using two models was conducted using the JMDC claims database (01/2005-01/2020). The onset of OAG: index date was defined as the diagnosis of glaucoma, prescription of anti-glaucoma drugs, or surgery of glaucoma. For each case, a maximum of 10 age-, sex-, and calendar year/month-matched controls were randomly selected by risk-set sampling with replacement. The number of statin prescriptions during the exposure assessment period, which was identified as the 12-month (model 1) or 24-month (model 2) periods prior to the index date, was used as an indicator for statin exposure. Adjusted odds ratios (aORs) and 95% confidence interval (CI) were estimated using conditional logistic regression analyses. We identified 375,373 patients with newly diagnosed dyslipidemia. Of these, 6180 cases and 61,792 controls (model 1) and 4153 cases and 41,522 controls (model 2) were selected. Statin use was not identified as a significant risk factor for OAG (model 1: aOR 0.98, 95% CI 0.93-1.03, model 2: aOR 0.97, 95% CI 0.91-1.04). Compared with nonexposure, short-term exposure (< 2 years) to statins was not related to an increased risk of OAG in the Japanese working-age population with dyslipidemia.
  • Noriaki Kataoka; Takeo Hata; Kouichi Hosomi; Atsushi Hirata; Emi Goto; Masami Nishihara; Teruo Inamoto; Haruhito Azuma; Masashi Neo
    International journal of clinical pharmacology and therapeutics 61 9 386 - 393 2023年07月 
    OBJECTIVE: To determine the safety of cabazitaxel and predictors of severe neutropenia caused by cabazitaxel in a patient population that includes those with comorbidities. MATERIALS AND METHODS: Of 42 prostate cancer patients treated with cabazitaxel at Osaka Medical and Pharmaceutical University Hospital between September 2014 and June 2022, 33 were included in this study, whereas 6 patients who were outpatients and 3 who were discharged early within 7 days upon patient request were excluded. Logistic regression analysis was used to examine predictors of severe neutropenia. RESULTS: Of the 33 eligible patients, 24 had comorbidities, with hypertension being the most common (n = 19), followed by dyslipidemia (n = 14) and diabetes (n = 11). There was no statistically significant difference in the rate of severe neutropenia due to any of the comorbidities, depending on the presence or absence of the comorbidity. However, the rate of severe neutropenia was significantly higher in patients with baseline platelet levels < 22.4×104/μL and those receiving cabazitaxel doses > 34 mg/body. In the final model adjusted for age, body mass index, C-reactive protein, and monocyte count, lower baseline platelet levels and higher doses of cabazitaxel were also predictors of the development of severe neutropenia. CONCLUSION: Comorbidities such as hypertension, dyslipidemia, diabetes mellitus, cerebrovascular disease, chronic kidney disease, liver dysfunction, and cardiac disease did not affect the incidence of severe neutropenia in patients receiving cabazitaxel. The baseline platelet count and the dose of cabazitaxel were also suggested to be markers for the development of severe neutropenia.
  • Yuika Komatsu; Masahiro Yodoshi; Manabu Takegami; Satoshi Yokoyama; Kouichi Hosomi
    International journal of clinical pharmacology and therapeutics 61 4 148 - 158 2023年04月 
    OBJECTIVE: The aim of this study was to investigate the risk of hemorrhage in concomitant therapy with direct oral anticoagulants (DOACs) and class IV antiarrhythmic drugs. MATERIALS AND METHODS: First, disproportionality analysis (DPA) was performed using the Japanese Adverse Drug Event Report (JADER) database to investigate the risk of hemorrhage with DOACs. Second, a cohort study was performed using electronic medical record data to confirm the results of the JADER analysis. RESULTS: In the JADER analysis, hemorrhage was significantly associated with treatment with edoxaban and verapamil (reporting odds ratio = 1.66; 95% confidence interval (CI) = 1.04 - 2.67). The cohort study revealed that hemorrhage incidence significantly differed between the verapamil-treated group and the bepridil-treated group, with a higher risk for hemorrhage in the verapamil group (log-rank test: p < 0.001). The multivariate Cox proportional hazards model also showed that the verapamil and DOAC combination was significantly associated with hemorrhage events compared with the bepridil and DOAC combination (hazard ratio (HR): 2.87, 95% CI: 1.17 - 7.07, p = 0.022). Furthermore, creatinine clearance (Ccr) ≥ 50 mL/min was significantly associated with hemorrhage events (HR: 2.72, 95% CI: 1.03 - 7.18, p = 0.043), and verapamil was significantly associated with hemorrhage in patients with Ccr ≥ 50 mL/min (HR: 3.58, 95% CI: 1.36 - 9.39, p = 0.010) but not in patients with Ccr < 50 mL/min. CONCLUSION: Verapamil increases the risk of hemorrhage in patients on DOACs. Dose adjustment of DOACs based on renal function may prevent hemorrhage when verapamil is concomitantly administered.
  • Satoshi Yokoyama; Kouichi Hosomi
    Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan 143 6 497 - 500 2023年 
    With the development of information technology, patient information is stored as electronic data, and huge amounts of such data are collected every day. Such a collection compiled over the course of clinical practice is called real-world data and is expected to be used for evaluating drug efficacy and safety. Real-world data such as health insurance association-based administrative claims databases, pharmacy-based dispensing databases, and spontaneous reporting system databases are mainly used in pharmaceutical research. Among them, claims databases are used for various observational studies such as studies on nationwide prescription trends, pharmacovigilance studies, and studies on rare diseases due to their large sample size. Although the nature of omics data is different from that of real-world data, it has become accessible on cloud platforms and are being used to broaden the scope of research in recent years. In this paper, we introduce a method for generating and further testing hypotheses through integrated analysis of real-world data and omics data, with a focus on administrative claims databases.
  • フィブラート系薬剤pemafibrateによる筋肉系障害に対するスタチン系薬剤併用の影響
    早川 萌風; 飯間 杏奈; 西田 美沙緒; 前川 頼子; 河渕 真治; 伊藤 由佳子; 上田 ひかる; 横山 聡; 細見 光一; 高田 充隆; 栄田 敏之
    日本臨床薬理学会学術総会抄録集 43回 1 - 010 (一社)日本臨床薬理学会 2022年12月
  • Takaya Uno; Kouichi Hosomi; Satoshi Yokoyama; Kazuyoshi Kawabata
    International journal of clinical pharmacology and therapeutics 2022年11月 
    OBJECTIVE: To identify the trends in tolvaptan prescription and the association between aging and tolvaptan-induced hypernatremia. MATERIALS AND METHODS: A health insurance claims database and a spontaneous adverse drug reaction database were used. RESULTS: Of all patients who had been prescribed tolvaptan, the proportion of patients aged 60 - 79 years and ≥ 80 years was consistent at ~ 40%. Moreover, the prescription frequency of tolvaptan increased over time for patients in the same age groups. The adjusted reporting odds ratio of tolvaptan-induced hypernatremia was 5.54 (95% confidence interval, 3.31 - 9.25) in patients aged ≥ 60 years from among all patients and 2.09 (95% confidence interval, 1.59 - 2.75) in those aged ≥ 80 years from among those aged ≥ 60 years. CONCLUSION: It may be necessary to be aware of hypernatremia in elderly patients who are expected to have increased prescriptions of tolvaptan.
  • Kaito Yamashiro; Mika Jouta; Kouichi Hosomi; Satoshi Yokoyama; Yuu Ozaki; Atsushi Hirata; Fumihiko Ogata; Takehiro Nakamura; Shigeharu Tanei; Naohito Kawasaki
    Scientific Reports 12 1 2022年10月 
    Abstract Microscopic colitis (MC) is a chronic inflammatory bowel disease that is characterized by nonbloody watery diarrhea. The epidemiology in Japan differs from that in Europe and the United States, but little information is available from epidemiological surveys of MC in Japan. This study aimed to provide a new hypothesis regarding the factors associated with MC by using the Japanese Adverse Drug Event Report (JADER) database. “Colitis microscopic” (preferred term code: 10056979) cases entered into the JADER database between 2004 and 2021 were analyzed. Of the 246,997 cases in the JADER database, 161 cases were observed to be associated with MC. A Weibull analysis revealed that the median onset duration of MC (interquartile range) was 72.5 (36.0‒125.5) days in lansoprazole users and 116.0 (60.3‒1089.0) days in aspirin users. A multiple logistic regression analysis revealed that MC was significantly associated with the female sex, as well as ages ≥ 60 years and drugs including lansoprazole, aspirin, and nicorandil. A subset analysis revealed that MC was positively associated with obesity in female cases. Our study cannot demonstrate a causal inference between MC and each drug; however, the findings suggest that MC was associated with nicorandil as well as with lansoprazole and aspirin.
  • Chihiro Nakagawa; Satoshi Yokoyama; Kouichi Hosomi
    The Annals of pharmacotherapy 57 6 10600280221126971 - 10600280221126971 2022年09月 
    BACKGROUND: Statins are expected to have beneficial effects on nonalcoholic fatty liver disease (NAFLD); however, evidence remains insufficient. OBJECTIVE: In this study, we aim to investigate the association between statin adherence and NAFLD development. METHODS: We conducted a nested case-control study of statin users using the Japan Medical Data Center administrative claims database (January 2005 to January 2020). Individuals who developed NAFLD were designated as cases. For each case, we randomly selected a maximum of 10 controls using risk set sampling. Good adherence was defined as the proportion of days covered (PDC) of ≥0.80. Higher intensity was defined as the median or higher of a cumulative defined daily dose (cDDD) per day covered by statin prescription. Conditional logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: In this study, 253 383 patients with the first statin prescription were identified. Of them, 7080 were selected and matched to 70 734 controls. The medians of PDC and intensity were 0.88 (interquartile range [IQR], 0.61-0.96) and 0.32 (IQR, 0.25-0.50) cDDD/day, respectively. Good adherence was significantly associated with a reduced risk of NAFLD development (adjusted OR, 0.82; 95% CI, 0.78-0.86). Higher intensity was not significantly associated with a reduced risk of NAFLD development (adjusted OR, 1.02; 95% CI, 0.97-1.08). CONCLUSION AND RELEVANCE: Good adherence to statins is associated with a reduced risk of NAFLD development, regardless of the statin intensity. Appropriate statin therapy could reduce the risk of NAFLD development.
  • Takaya Uno; Mitsutaka Takada; Satoshi Yokoyama; Kazuyoshi Kawabata; Kouichi Hosomi
    International journal of clinical pharmacology and therapeutics 60 11 477 - 485 2022年09月 
    OBJECTIVE: Calcineurin inhibitors (CNIs), including cyclosporine and tacrolimus, are associated with an increased cancer risk. However, whether mammalian target of rapamycin inhibitors (mTORis), including sirolimus and everolimus, decrease the cancer risk in patients receiving CNIs remains uncertain. We aimed to determine whether mTORis are associated with a decreased cancer risk in patients receiving CNIs using data mining of a spontaneous adverse reaction database. MATERIALS AND METHODS: Disproportionality analysis was conducted using the U.S. Food and Drug Administration Adverse Event Reporting System database (2004 - 2019) with reporting odds ratio and information component being used to indicate a signal. RESULTS: Data subset analyses indicated that sirolimus and everolimus were not associated with a decreased cancer risk in patients receiving cyclosporine or tacrolimus but were associated with an increased risk of nonmelanoma skin cancer (NMSC) and Kaposi's sarcoma. CONCLUSION: mTORis are not associated with a decreased cancer risk but are associated with a further increase in the risk of NMSC and Kaposi's sarcoma in patients receiving CNIs. Further studies are necessary to clarify the mechanism underlying the association between mTORis and NMSC or Kaposi's sarcoma.
  • K Yamashiro; K Hosomi; S Yokoyama; F Ogata; T Nakamura; N Kawasaki
    Die Pharmazie 77 7 243 - 247 2022年09月 
    Proton pump inhibitors (PPIs) are commonly used for the prevention or treatment of gastric ulcers, but they can induce hypomagnesemia. Little is known about the onset duration and risk factors related to patient characteristics of this adverse event in Japanese patients. Therefore, we analyzed the time-to-onset of PPI-induced hypomagnesemia and evaluated the association between hypomagnesemia and PPIs using the Japanese Adverse Drug Event Report (JADER) database. We analyzed hypomagnesemia cases between 2004 and 2021. The time-to-onset analysis was performed using the Weibull distribution, and the adjusted reporting odds ratio (aROR) or 95% confidence interval (95% CI) was calculated using a multiple logistic regression analysis. The analysis database comprised 236,525 cases, with 188 cases associated with hypomagnesemia. The median onset duration (interquartile range) of PPI-induced hypomagnesemia was 99.0 (51.8-285.5 ) days, which is considered the random failure type. The multiple logistic regression analysis revealed that hypomagnesemia is significantly associated with male sex (aROR, 95% CI: 1.66, 1.23-2.25) , age < 60 (1.59, 1.14-2.21) , estimated body-mass index (eBMI) (0.94, 0.91-0.98) , PPIs (1.66, 1.18-2.30) , and the interaction of age (<60)*PPIs (1.58, 1.13-2.19) . However, diuretics were not significantly associated with hypomagnesemia. Our results suggest that serum magnesium levels should be measured regularly regardless of the duration of PPI use, especially in patients with male sex, age < 60, or low BMI. These findings will assist health professionals in the adequate use of PPIs. These findings need to be evaluated by cohort studies and long-term clinical investigations.
  • Yuika Komatsu; Satoshi Yokoyama; Kouichi Hosomi; Mitsutaka Takada
    Drugs - real world outcomes 9 3 437 - 449 2022年09月 
    BACKGROUND: Atrial fibrillation (AF) is a major risk factor for the development of stroke and silent cerebral infarct (SCI). Additionally, AF is independently associated with neurological disorders, including cognitive impairment and dementia. Although oral anticoagulants (OACs) are used to reduce the risk of development of stroke and SCI in patients with AF, it is unclear whether OACs reduce the risk of dementia. OBJECTIVE: This study aimed to investigate the association between OAC use and dementia in relatively young patients with AF. Moreover, the impact of medication adherence on the association between OAC use and the risk of dementia was examined. PATIENTS AND METHODS: This retrospective cohort study was conducted using a large claims database-Japan Medical Data Center, Inc. (JMDC)-from which newly diagnosed patients with AF younger than 75 years of age were identified. We analyzed medication adherence using the medication possession ratio (MPR). The dementia risk was compared between the OAC and non-OAC groups using Cox proportional hazards regression analysis and the Kaplan-Meier method after propensity score matching. Similarly, the MPR-classified and non-OAC groups were also compared. RESULTS: OAC administration was not associated with the risk of dementia in the entire cohort (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.40-1.08; p = 0.098); however, OAC administration in patients with an MPR ≥90% was significantly associated with a lower risk of dementia (HR 0.45, 95% CI 0.25-0.81; p = 0.008). Meanwhile, direct OAC (DOAC) and warfarin (WF) administration was not associated with the risk of dementia regardless of MPR. Kaplan-Meier analysis revealed a significant difference in the incidence of dementia between the MPR ≥ 90% OAC and non-OAC groups (log-rank test: p = 0.006). However, no difference was observed in the incidence of dementia between the MPR ≥ 90% WF and non-OAC groups, or between the MPR ≥ 90% DOAC and non-OAC groups. CONCLUSIONS: OAC administration was not associated with the risk of dementia in relatively young patients with AF; however, when limited to patients with an MPR ≥ 90%, OAC administration reduced the risk of dementia. Our results suggest that the association between OAC use and dementia should be evaluated while considering medication adherence.
  • コロナ禍の多職種連携教育における仮想空間実施の影響
    池田 行宏; 木村 貴明; 三井 良之; 藤田 貢; 梶 博史; 赤木 將男; 松村 到; 井上 知美; 細見 光一; 大鳥 徹; 小竹 武; 岩城 正宏
    医学教育 53 Suppl. 233 - 233 (一社)日本医学教育学会 2022年07月
  • コロナ禍の多職種連携教育における仮想空間実施の影響
    池田 行宏; 木村 貴明; 三井 良之; 藤田 貢; 梶 博史; 赤木 將男; 松村 到; 井上 知美; 細見 光一; 大鳥 徹; 小竹 武; 岩城 正宏
    医学教育 53 Suppl. 233 - 233 (一社)日本医学教育学会 2022年07月
  • 有害事象自発報告データベース(JADER)を用いたプロトンポンプ阻害薬による低マグネシウム血症の有害事象プロファイルの評価
    山城 海渡; 細見 光一; 横山 聡; 緒方 文彦; 中村 武浩; 川崎 直人
    日本薬学会年会要旨集 142年会 26F - pm08S (公社)日本薬学会 2022年03月
  • 電子カルテデータを用いた直接経口抗凝固薬と経口抗不整脈薬の併用による出血リスクに関する研究
    小松 唯可; 吉年 正宏; 淺野 肇; 柳江 正嗣; 竹上 学; 横山 聡; 細見 光一
    日本薬学会年会要旨集 142年会 26F - pm09S (公社)日本薬学会 2022年03月
  • レセプトデータベースを用いたSGLT2阻害薬と膵がんとの関連性についての研究
    田中 侑希; 横山 聡; 細見 光一
    日本薬学会年会要旨集 142年会 26PO1 - 13S (公社)日本薬学会 2022年03月
  • フィブラート系薬剤投与に伴う横紋筋融解症に対するスタチン系薬剤併用の影響
    大淵 亜美; 土井 彩奈; 大坂 歩; 飯間 杏奈; 河渕 真治; 伊藤 由佳子; 上田 ひかる; 横山 聡; 細見 光一; 高田 充隆; 栄田 敏之
    日本薬学会年会要旨集 142年会 27PO5 - 07S (公社)日本薬学会 2022年03月
  • 抗精神病薬と関節リウマチの関連性の検討 バイオインフォマティクスデータベースを活用したドラッグリポジショニング
    中川 千拓; 横山 聡; 細見 光一
    日本薬学会年会要旨集 142年会 28PO6 - 05S (公社)日本薬学会 2022年03月
  • 「医療ビッグデータ×AI×臨床」医療の発展に貢献するデータサイエンス レセプトデータベースを中心としたビッグデータの利活用
    横山 聡; 細見 光一
    日本薬学会年会要旨集 142年会 S31 - 3 (公社)日本薬学会 2022年03月
  • Satoshi Yokoyama; Chihiro Nakagawa; Kouichi Hosomi
    Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 30 2 1765 - 1773 2022年02月 
    PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse event of cancer treatment; however, no drug is recommended for the prevention of CIPN. In Japan, several drugs such as Gosha-Jinki-Gan and duloxetine are frequently administered as a treatment for CIPN. The aim of this study was to elucidate prescription patterns of drugs administered for CIPN caused by oxaliplatin and the association between these drugs and the duration of oxaliplatin treatment. METHODS: We conducted a retrospective nationwide study using the JMDC administrative claims database (January 2005-June 2020; JMDC Inc., Japan). Patients newly treated with oxaliplatin were identified, and prescription patterns of CIPN medication including Gosha-Jinki-Gan, pregabalin, duloxetine, mecobalamin, and mirogabalin were investigated. The primary outcome was the duration of oxaliplatin treatment. Multivariable logistic regression analysis was performed to examine the association between CIPN medication and duration of oxaliplatin treatment. RESULTS: A total of 4,739 patients who newly received oxaliplatin were identified. Of these, 759 (16.0%) had received CIPN medication. Duloxetine was administered in 99 (2.1%) patients. Multivariable logistic regression analysis revealed that CIPN medication was significantly associated with the prolonged duration of oxaliplatin treatment (odds ratio: 2.35, [95% confidence interval: 1.99-2.77]). CONCLUSION: Real-world data demonstrated that the administration rate of CIPN medication was higher in patients who received oxaliplatin treatment for over 6 months.
  • 家田 正子; 宮本 朋佳; 細見 光一; 竹上 学; 川畑 篤史
    薬局薬学 advpub 一般社団法人 日本薬局学会 2022年 
    【背景・目的】薬学部生は実務実習期間中，多くの医薬品を「商品名」で学ぶため，大学で習得した「一般名」の知識が実習後に低下する可能性が懸念される．そこで実務実習前後に「一般名」と「商品名」の理解度に関するテストを実施し，結果に影響を与える因子を解析した．【方法】近畿大学病院で実務実習に参加した学生64名を対象に，実習前，薬局実習後，病院実習後に「一般名」または「商品名」で表示された薬の薬理作用に対する知識を測るマークシート形式のテストを行った．【結果】実務実習により薬の「商品名」に関する知識が有意に上昇した一方，「一般名」に関する知識は変化しなかった．【考察】実務実習後，懸念されたほど薬の「一般名」に関する知識は低下していなかったが，実習期間中に「商品名」と「一般名」をリンクさせる学習を行うことが，大学で習得した知識を生かした調剤や処方解析を行うために役立つと考えられた．
  • Shoko Ieda; Tomoyoshi Miyamoto; Kouichi Hosomi; Manabu Takegami; Atsufumi Kawabata
    Journal of palliative medicine 25 4 570 - 576 2021年10月 
    Background: Accurate prognosis in terminal cancer patients is useful to improve their quality of life and also to decide the cessation of fluid administration. Nonetheless, few prognostic indicators are available for prediction of such a short-term life expectancy. Objectives: The present study aimed at evaluating the efficacy of C-reactive protein (CRP)/albumin (CRP/Alb) ratio, prognostic nutritional index (PNI), fibrosis-4 (FIB-4) index, and albumin-bilirubin (ALBI) score in identifying terminal cancer patients who have a life expectancy less than two weeks. Design: Retrospective study. Setting/Subjects: Of 483 patients who died between April 2019 and March 2020 at a single center in Japan, 102 who met the inclusion criteria were enrolled in this study. Measurements: CRP/Alb, PNI, FIB-4, and ALBI were calculated from the laboratory data collected 1-13, 14-27, 28-83, and 168-365 days before death and subjected to statistical analyses. Results: CRP/Alb, PNI, FIB-4, and ALBI values were significantly associated with the time before death during terminal 365 days. CRP/Alb ≥4.4, PNI <30, FIB-4 ≥ 9.4, and ALBI ≥ -1.26 were significantly associated with the transition from the first half to the second half of terminal four weeks. Of those prognostic indicators, three and four combinations provided significantly reliable estimation of a life expectancy less than two weeks. Conclusions: CRP/Alb, PNI, FIB-4, ALBI, and their combinations are considered to help identify cancer patients who have a life expectancy less than two weeks, which is useful to make appropriate end-stage treatment decisions, for example, cessation of artificial hydration therapy.
  • Takayuki Mabuchi; Kouichi Hosomi; Satoshi Yokoyama; Mitsutaka Takada
    International journal of clinical pharmacology and therapeutics 59 5 353 - 357 2021年05月 
    A retrospective data analysis was performed to investigate the association between polypharmacy and adverse events using three different spontaneous adverse event reporting system databases. Multivariate logistic regression analyses were performed to investigate the association between the number of drugs and adverse events, including hepatic disorders, renal disorders, hypersensitivity, and extrapyramidal syndrome. The results showed that the risk of hepatic and renal disorders increased with the number of drugs. Thus, decreasing the number of drugs may reduce the risk of hepatic and renal disorders. Furthermore, attention should be given to specific drugs that may cause hypersensitivity and extrapyramidal syndrome.
  • フィブラート系薬剤の有害事象発現リスクに対するスタチン系薬剤併用の影響
    杉山 大介; 山嵜 伊織; 重村 敦史; 河渕 真治; 伊藤 由佳子; 上田 ひかる; 横山 聡; 細見 光一; 高田 充隆; 栄田 敏之
    日本薬学会年会要旨集 141年会 29V07 - pm02S (公社)日本薬学会 2021年03月
  • 服薬アドヒアランスを考慮した経口抗凝固薬における認知症リスクに関する研究
    小松 唯可; 細見 光一; 横山 聡; 高田 充隆
    日本薬学会年会要旨集 141年会 27P02 - 213S (公社)日本薬学会 2021年03月
  • レセプトデータを用いたSGLT2阻害薬と大腸がんとの関連性についての研究
    田中 侑希; 横山 聡; 細見 光一; 高田 充隆
    日本薬学会年会要旨集 141年会 27P02 - 262S (公社)日本薬学会 2021年03月
  • Chihiro Nakagawa; Satoshi Yokoyama; Kouichi Hosomi; Mitsutaka Takada
    Therapeutic advances in musculoskeletal disease 13 1759720X211047057  2021年 
    INTRODUCTION: Treatment of rheumatoid arthritis (RA) has advanced with the introduction of biological disease-modifying antirheumatic drugs. However, more than 20% of patients with RA still have moderate or severe disease activity. Hence, novel antirheumatic drugs are required. Recently, drug repurposing, a process of identifying new indications for existing drugs, has received great attention. Furthermore, a few reports have shown that antipsychotics are capable of affecting several cytokines that are also modulated by existing antirheumatic drugs. Therefore, we investigated the association between antipsychotics and RA by data mining using real-world data and bioinformatics databases. METHODS: Disproportionality and sequence symmetry analyses were employed to identify the associations between the investigational drugs and RA using the US Food and Drug Administration Adverse Event Reporting System (2004-2016) and JMDC administrative claims database (January 2005-April 2017; JMDC Inc., Tokyo, Japan), respectively. The reporting odds ratio (ROR) and information component (IC) were used in the disproportionality analysis to indicate a signal. The adjusted sequence ratio (SR) was used in the sequence symmetry analysis to indicate a signal. The bioinformatics analysis suite, BaseSpace Correlation Engine (Illumina, CA, USA) was employed to explore the molecular mechanisms associated with the potential candidates identified by the drug-repurposing approach. RESULTS: A potential inverse association between the antipsychotic haloperidol and RA, which exhibited significant inverse signals with ROR, IC, and adjusted SR, was found. Furthermore, the results suggested that haloperidol may exert antirheumatic effects by modulating various signaling pathways, including cytokine and chemokine signaling, major histocompatibility complex class-II antigen presentation, and Toll-like receptor cascade pathways. CONCLUSION: Our drug-repurposing approach using data mining techniques identified haloperidol as a potential antirheumatic drug candidate.
  • Satoshi Yokoyama; Yuki Tanaka; Kouichi Hosomi; Mitsutaka Takada
    International journal of medical sciences 18 15 3574 - 3580 2021年 
    Background: Amiodarone is rich in iodine, so in clinical practice amiodarone-induced hypothyroidism (AIH) is a major side effect. This drug is used in patients with arrhythmias, especially atrial fibrillation, the most common sustained arrhythmia. Polypharmacy, which can result in complex drug-drug interactions, occurs in more than 70% of the patients with atrial fibrillation. Therefore, polypharmacy may be involved in the expression of AIH. In this study, we investigated the association between polypharmacy and AIH. Methods: We conducted a retrospective study using data from January 2006 to May 2020 collected from a large, organized database of prescriptions constructed by the Japan Medical Information Research Institute, Inc. (Tokyo, Japan). To investigate the association between number of prescribed drugs with amiodarone and AIH, we divided patients into two groups: polypharmacy (≥ 5 prescribed drugs) and non-polypharmacy (< 5 prescribed drugs). We then performed a sequence symmetry analysis on the two groups: incident thyroxine after incident amiodarone and incident thyroxine before incident amiodarone. Finally, we conducted a case-control study on two further groups: those prescribed thyroxine after incident amiodarone (AIH group; n=555) and those not prescribed thyroxine after incident amiodarone (non-AIH group; n=6,192). Results: Sequence symmetry analysis revealed a significant association between amiodarone and thyroxine in both the polypharmacy and non-polypharmacy groups. The ranges for the adjusted sequence ratio in the two groups were 12.0-16.7 and 7.3-9.0, respectively. The case-control study showed that ≥5 prescribed drugs at the first prescription of amiodarone were found to significantly increase the odds of AIH (odds ratio: 1.48, 95% confidence interval: 1.18-1.84). Conclusion: Polypharmacy was suggested as an independent risk factor for AIH. Careful assessment of the appropriateness of prescription is warranted.
  • Kazuki Matsui; Yutaro Mukai; Kota Sakakura; Kyoichi Wada; Tsutomu Nakamura; Atsufumi Kawabata; Nobue Terakawa; Naoki Hayakawa; Kengo Kusano; Kouichi Hosomi; Satoshi Yokoyama; Mitsutaka Takada
    International journal of clinical pharmacology and therapeutics 59 1 63 - 70 2021年01月 
    OBJECTIVE: Bepridil prolongs the QT interval and can induce torsade de pointes. Although increased bepridil concentration may be a primary cause of prolonged QT, the relationship between serum bepridil concentration and prolonged QT remains unclear. We investigated the relationship between serum bepridil concentration and the corrected QT (QTc) interval in patients treated with bepridil. MATERIALS AND METHODS: A retrospective study was performed at the National Cerebral and Cardiovascular Center in Japan. Patients with atrial fibrillation who were treated with bepridil from January 2014 to December 2015 were enrolled in the study. Serum bepridil concentrations and electrocardiogram data collected more than 21 days after the initiation of bepridil were used for analysis. RESULTS: A total of 60 patients were included in this study. There was a significant difference in mean QTc interval before and after initiation of bepridil (p < 0.0001). A significant relationship was observed between bepridil dose (p = 0.014) or serum bepridil concentration (p < 0.001) and QTc interval. Additionally, a significant relationship was observed between serum bepridil concentration and ΔQTc (p = 0.034). In the study, 4 patients developed QTc prolongation ≥ 500 ms after the initiation of bepridil. Serum bepridil concentration in this group was significantly higher compared with the group that did not display prolonged QTc (973 ± 651 vs. 526 ± 310 ng/mL, p = 0.01). CONCLUSION: This study revealed that the QTc interval was significantly associated with serum bepridil concentration. Serum bepridil concentration beyond a therapeutic range may be a critical risk factor for developing QTc prolongation.
  • Takayuki Mabuchi; Kouichi Hosomi; Satoshi Yokoyama; Mitsutaka Takada
    International journal of clinical pharmacology and therapeutics 58 11 601 - 607 2020年11月 [査読有り]
     
    OBJECTIVE: Polypharmacy has become a major problem in medical care worldwide, including in Japan. The purpose of this study was to investigate the current situation of polypharmacy using different spontaneous adverse drug event report databases. MATERIALS AND METHODS: A retrospective data analysis was performed using reports from 2007 to 2015 from three different spontaneous adverse drug event report databases: the Japanese Adverse Drug Event Report (JADER) constructed by the Pharmaceuticals and Medical Devices Agency in Japan, the US Food and Drug Administration (FDA) Adverse Drug Event Reporting System (FAERS) constructed by the FDA in the United States, and the Canada Vigilance Adverse Reaction Online Database (CVARD) constructed by the government of Canada. Polypharmacy trends during the study period were investigated. RESULTS: The mean numbers of drugs per report in the JADER, FAERS, and CVARD databases during the study period were 6.62, 3.76, and 3.44, respectively. The mean number of drugs per report increased with age in all three databases, with a peak at ages 70 - 79 years in all three databases (7.0 drugs for JADER, 4.7 drugs for FAERS, and 4.2 drugs for CVARD). CONCLUSION: Adverse event reports were more likely to develop in the patients treated through polypharmacy. Polypharmacy in Japan should be improved to prevent adverse events. Additionally, the patients aged ≥ 80 years tended to develop adverse events even if the number of prescribed drugs was relatively small. Therefore, polypharmacy should be noted in these patients to prevent adverse events.
  • Satoshi Yokoyama; Shoki Wakamoto; Yuki Tanaka; Chihiro Nakagawa; Kouichi Hosomi; Mitsutaka Takada
    ANNALS OF PHARMACOTHERAPY 54 10 988 - 995 2020年10月 [査読有り]
     
    Background: Osteoporosis, which is a major public health concern, has been known to reduce health-related quality of life. Some studies have suggested that antipsychotics could perhaps cause osteoporosis by increasing serum prolactin levels. However, the association between antipsychotics and the risk for developing osteoporosis has been controversial. Objective: The present study aimed to assess the association between antipsychotic use and onset of osteoporosis in real-world settings. Methods: A multimethod data-mining approach using different algorithms and databases was used. First, disproportionality analysis was conducted using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database (2004-2017) with reporting odds ratio (ROR) and information component (IC) being used to indicate a signal. Furthermore, a sequence symmetry analysis using data from a large Japanese administrative claims database (2005-2017; JMDC Inc, Japan) was conducted. Short-term intervals (ie, 12, 24, and 36 months) were set to investigate the association between antipsychotic use and onset of osteoporosis using the adjusted sequence ratio (SR) to indicate a signal. Results: No potential association between osteoporosis and all antipsychotics was observed in the FAERS database, except for perphenazine, which exhibited significant signals using both ROR and IC. Moreover, no potential association between osteoporosis and antipsychotics was observed in the JMDC claims database, except for sulpiride and aripiprazole. None of the antipsychotics indicated significant signals using all analyzed items (ROR, IC, and adjusted SR). Conclusion and Relevance: Real-world data show no association between antipsychotic use and the onset of osteoporosis. Further pharmacoepidemiological studies are needed for causality assessment.
  • Takayuki Mabuchi; Kouichi Hosomi; Satoshi Yokoyama; Mitsutaka Takada
    Journal of clinical pharmacy and therapeutics 45 5 991 - 996 2020年10月 [査読有り]
     
    WHAT IS KNOWN AND OBJECTIVE: Polypharmacy is associated with an increased risk of adverse drug reactions (ADRs) and drug interactions, decreased adherence to medication and increased medical cost. Recently, polypharmacy has become a major problem in medical care in Japan as a result of the increase in the ageing population. The purpose of this study was to investigate the current situation of polypharmacy and the association between polypharmacy and adverse events. METHODS: A retrospective data analysis was performed using two different real-world data from 2007 to 2015 in Japan. The Japanese Adverse Drug Event Report (JADER), a public spontaneous adverse drug reaction database constructed by the Pharmaceuticals and Medical Devices Agency (PMDA), and a large prescription database constructed by a database vendor (Japan Medical Information Research Institute, Inc Japan [JMIRI]) were analysed. Trends of polypharmacy during the study period were investigated. RESULTS AND DISCUSSION: The mean number of drugs per report in the JADER database and per prescription in the JMIRI databases during the study period ranged from 4.8 to 5.6 and 3.5 to 3.7, respectively. The mean number of drugs increased with age in both the JADER and JMIRI databases, and the peak of the mean number of drugs was at 80-89 years (5.74 drugs) in the JADER database and at 90-99 years (4.97 drugs) in the JMIRI database. WHAT IS NEW AND CONCLUSIONS: The number of drugs increased until age 90 years or more, even though adverse events are more likely to occur after the age of 80 in Japan. Therefore, polypharmacy in the elderly should be focused on the patients aged ≥80 years rather than patients aged ≥65 years from the viewpoint of the prevention of adverse events.
  • Ryosuke Ota; Atsushi Hirata; Keisuke Noto; Satoshi Yokoyama; Kouichi Hosomi; Mitsutaka Takada; Hiroshi Matsuoka
    INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS 58 5 274 - 281 2020年05月 [査読有り]
     
    Objective: The relationship between serum creatinine and calcium (Ca) was investigated in hematopoietic stem cell transplantation (HSCT) patients treated with foscarnet. Materials and methods: A retrospective study was performed to investigate the development of foscarnet-induced renal dysfunction in patients who received HSCT from April 2010 to November 2018 at the Kindai University Nara Hospital. A total of 80 patients were identified from the medical records, and 42 patients who met the inclusion criteria were enrolled in this study. Renal dysfunction was classified according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Results: A significant inverse relationship was observed between serum creatinine and Ca levels (r = -0.372; p < 0.0001; y = -0.537x + 9.268). A separate analysis divided into renal dysfunction and non-renal dysfunction groups showed that there was a significant relationship between serum creatinine and Ca levels in the renal dysfunction group (r = -0.531: p < 0.0001; y = -0.617x + 9.239) but not in the non-renal dysfunction group (r = -0.011; p = 0.561; y = -0.023x + 8.934). The optimal cutoff for the minimum Ca level was calculated to be 8.1 mg/mL. Conclusion: A significant inverse relationship was observed between serum creatinine and Ca levels in HSCT patients with foscarnet-induced renal dysfunction. Foscarnet-induced renal dysfunction should be noted if Ca levels fall below 8.1 mg/dL. Monitoring Ca levels may be useful for detecting renal dysfunction at early stages in patients treated with foscarnet.
  • Iwasawa M; Sagami K; Yokoyama S; Hosomi K; Takada M
    International journal of clinical pharmacology and therapeutics 58 4 214 - 222 2020年04月 [査読有り]
     
    OBJECTIVE: The purpose of this study was to examine whether co-initiation of antiulcer drugs (AUDs) and low-dose aspirin (LDA) therapy is beneficial for good adherence to LDA therapy. MATERIALS AND METHODS: A retrospective cohort study was conducted using the JMDC claims database. Patients for whom LDA therapy was newly initiated between January 2005 and April 2016 were selected from the JMDC database. The selected patients were divided into LDA and LDA+AUD groups and were followed up from the first prescription of LDA or LDA+AUD until the earliest of the following events: discontinuation or the end of the observation period. Unadjusted and multivariable Cox proportional hazards models controlling for all demographic and clinical characteristics were applied to examine whether the addition of an AUD to LDA improved adherence. A 1 : 1 propensity score matching analysis was conducted to balance confounders between the two groups. RESULTS: After the propensity score matching analysis, 4,089 patients were matched in each therapy group. The Kaplan-Meier curves for the rate of LDA continuation showed a sharp decline just after the initiation of LDA therapy. A significant difference was observed in the incidence of LDA therapy discontinuation between the LDA+AUD and LDA groups (HR: 0.87, 95% CI: 0.82 - 0.92), and the median duration of LDA therapy in the LDA+AUD and LDA groups were 18 and 11 months (log-rank test: p < 0.0001), respectively. CONCLUSION: The therapy persistence rate in the LDA+AUD group was significantly higher than that in the LDA group.
  • Ryo Inose; Natsue Hashimoto; Kouichi Hosomi; Satoshi Yokoyama; Mitsutaka Takada
    International journal of clinical pharmacology and therapeutics 58 3 131 - 138 2020年03月 [査読有り]
     
    OBJECTIVE: This study was aimed at investigating the risk of malignancies in rheumatoid arthritis patients treated with methotrexate (MTX), and whether the addition of biological disease-modifying antirheumatic drugs (bDMARDs) further increases the risk of malignancies in patients receiving MTX therapy, by using data from a spontaneous adverse reaction database. MATERIALS: Patient data from the U.S. Food and Drug Administration's Adverse Event Reporting System (FAERS) from the first quarter of 2004 to the end of 2015 were analyzed. METHODS: A data subset analysis was performed to investigate whether the use of bDMARDs further increased the risk of malignancies in patients receiving MTX therapy. RESULTS: MTX showed significant associations with all malignancies except liver cancer. bDMARDs showed significant associations with stomach cancer, colorectal cancer, prostate cancer, ovarian cancer, malignant melanoma, and lung cancer. In addition, bDMARD use increased the risk of breast, ovarian, and lung cancers in rheumatoid arthritis patients receiving MTX therapy. CONCLUSION: MTX use was significantly associated with various malignancies. Moreover, concomitant use of bDMARDs further increased the risk of breast, ovarian, and lung cancers in MTX-treated patients with rheumatoid arthritis.
  • Sayoko Kinoshita; Kouichi Hosomi; Satoshi Yokoyama; Mitsutaka Takada
    Journal of clinical pharmacy and therapeutics 45 1 65 - 71 2020年02月 [査読有り]
     
    WHAT IS KNOWN AND OBJECTIVE: Amiodarone (AMD) treatment is associated with a number of significant adverse effects including thyroid dysfunction. However, the relationship between the development of thyroid dysfunction and the dosage and treatment duration of AMD remains unclear. The purpose of this study was to examine the onset profiles of amiodarone-associated thyroid dysfunction using a spontaneous adverse drug reaction (ADR) reporting database. METHODS: Data were obtained from the US Food and Drug Administration Adverse Event Reporting System (FAERS). For signal detection of spontaneous ADRs, the reporting odds ratio (ROR) and information component (IC) were calculated. Cumulative incidences of hyperthyroidism and hypothyroidism were assessed using the Kaplan-Meier method, and time-to-onset profiles were analysed using the Weibull shape parameter (WSP) test. RESULTS AND DISCUSSION: The median time-to-onset of hyperthyroidism associated with AMD and other drugs was 720.0 (range: 225.5-1145.0) and 101.5 (range: 14.0-468.8) days, respectively. Patients treated with AMD showed a significantly longer time-to-onset of hyperthyroidism than those treated with other drugs (P < .001). The median time-to-onset of hypothyroidism associated with AMD and other drugs was 183.0 (range: 35.0-727.8) and 153.0 (range: 19.0-608.0) days, respectively. There was no significant difference in the time-to-onset of hypothyroidism between patients treated with AMD and those treated with other drugs (P = .13). For hyperthyroidism, the WSP test showed that AMD had a wear-out failure-type profile and other drugs had early failure-type profiles. For hypothyroidism, the WSP test showed that both AMD and other drugs had early failure-type profiles. WHAT IS NEW AND CONCLUSIONS: Amiodarone-associated hyperthyroidism had a different onset profile than hyperthyroidism associated with other drugs. Because the time-to-onset of AMD-associated hyperthyroidism is widely distributed, sustained and continuous attention is required to detect and treat hyperthyroidism during AMD treatment. In contrast, AMD-associated hypothyroidism had an onset profile that was similar to that of other drugs, suggesting that attention should be focused on the earlier stages of treatment.
  • Satoshi Yokoyama; Shoko Ieda; Mirai Nagano; Chihiro Nakagawa; Makoto Iwase; Kouichi Hosomi; Mitsutaka Takada
    INTERNATIONAL JOURNAL OF MEDICAL SCIENCES 17 4 471 - 479 2020年 [査読有り]
     
    Introduction: Warfarin and direct oral anticoagulants (DOACs) have been widely used in antithrombotic therapy. Although warfarin use has been suspected to be associated with osteoporosis risk, several studies have shown otherwise. Conversely, a few reports have found an association between DOACs and osteoporosis. This study therefore clarifies the association between oral anticoagulants and osteoporosis by analyzing real-world data using different methodologies, algorithms, and databases.Methods: Real-world data from the US Food and Drug Administration Adverse Event Reporting System (FAERS; 2004-2016) and Japanese administrative claims database (2005-2017; JMDC Inc., Tokyo) were used. Reporting odds ratio (ROR) and information component (IC) were calculated through disproportionality analysis (DPA) using reports recorded in the FAERS. Sequence symmetry analysis (SSA) was employed to calculate the adjusted sequence ratio (SR) using the JMDC Claims Database. For the adjusted SR and ROR, a significant signal was detected when the lower limit of the two-sided 95% confidence interval (CI) was more than 1. For the IC, a significant signal was detected when the lower limit of the 95% CI was more than 0.Results: DPA for warfarin found significant signals for osteoporosis in ROR (1.43, 95% CI: 1.32-1.54) and IC (0.50, 95% CI: 0.39-0.61). SSA showed a significant association between warfarin use and osteoporosis or bisphosphonate use. Moreover, a significant association was observed in males and females, albeit only for warfarin.Conclusion: Multi-methodological data mining revealed that warfarin use, not DOACs, is significantly associated with osteoporosis regardless of sex difference.
  • Sayoko Kinoshita; Kouichi Hosomi; Satoshi Yokoyama; Mitsutaka Takada
    International journal of medical sciences 17 3 302 - 309 2020年 [査読有り]
     
    Background: The association between metformin and amiodarone-induced adverse events was examined using spontaneous adverse event database. Additionally, the association between other antidiabetic drugs and amiodarone-induced adverse events were also examined. Methods: A total of 6,153,696 reports from the first quarter of 2004 through the fourth quarter of 2015 were downloaded from the US Food and Drug Administration adverse event reporting system. Reporting odds ratio (ROR) and information component (IC) were used to detect associations between antidiabetic drugs and amiodarone-associated adverse events. Additionally, subset data analysis was performed to investigate whether the use of antidiabetic drugs further increased or decreased the risk of adverse events in patients receiving amiodarone therapy. Next, the RORs were adjusted for coadministered antidiabetic drugs using logistic regression analysis. Results: By whole dataset analysis, significant inverse associations were found between metformin and interstitial lung disease (ROR 0.84, 95% confidence interval [CI] 0.79-0.90; IC -0.24, 95% CI -0.33 to -0.15). In the subset data analysis, metformin (ROR 0.62, 95%CI 0.43-0.89; IC -0.63, 95%CI -1.14 to -0.11), sulfonylureas (ROR 0.53, 95%CI 0.32-0.85; IC -0.85, 95%CI -1.53 to -0.17), and dipeptidyl peptidase-4 (DPP-4) inhibitors (ROR 0.25, 95%CI 0.08-0.78; IC -1.66, 95%CI -3.08 to -0.23) were inversely associated with hyperthyroidism. Additionally, metformin (ROR 0.43, 95%CI 0.33-0.57; IC -1.09, 95%CI -1.49 to -0.69), sulfonylureas (ROR 0.64, 95%CI 0.48-0.86; IC -0.59, 95%CI -1.00 to -0.17), and DPP-4 inhibitors (ROR 0.47, 95%CI 0.27-0.81; IC -0.99, 95%CI -1.76 to -0.22) were inversely associated with interstitial lung disease. In the logistic regression analyses, DPP-4 inhibitors (adjusted ROR 0.32, 95% CI 0.10-1.00) and metformin (adjusted ROR 0.46, 95% CI 0.34-0.62) were inversely associated with amiodarone-associated hyperthyroidism and interstitial lung disease, respectively. Conclusion: Metformin is a candidate drug to reduce the risk of amiodarone-induced hyperthyroidism and interstitial lung disease.
  • Takaya Uno; Kyoichi Wada; Kouichi Hosomi; Sachi Matsuda; Megumi Morii Ikura; Hiromi Takenaka; Nobue Terakawa; Akira Oita; Satoshi Yokoyama; Atsushi Kawase; Mitsutaka Takada
    EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY 76 1 117 - 125 2020年01月 [査読有り]
     
    Purpose This study investigated the effects of clotrimazole troche on the risk of transplant rejection and the pharmacokinetics of tacrolimus. Methods The data mining approach was used to investigate whether the use of clotrimazole increased the risk of transplant rejection in patients receiving tacrolimus therapy. Patient data were acquired from the US Food and Drug Administration's Adverse Event Reporting System (FAERS) from the first quarter of 2004 to the end of 2017. Next, we retrospectively investigated the effect of clotrimazole troche on tacrolimus pharmacokinetics in seven patients who underwent heart transplantation between March and December 2017. Results The FAERS subset data indicated a significant association between transplant rejection and tacrolimus with clotrimazole [reporting odds ratio 1.92, 95% two-sided confidence interval (95% CI) 1.43-2.58, information component 0.81, 95% CI 0.40-1.23]. The pharmacokinetic study demonstrated a significant correlation between trough concentration (C-0) and area under the concentration-time curve of tacrolimus after discontinuation of clotrimazole (R-2 = 0.60, P < 0.05) but not before its discontinuation. Furthermore, the median clearance/bioavailability of tacrolimus after discontinuation of clotrimazole was 2.2-fold greater than that before its discontinuation (0.27 vs. 0.59 L/h/kg, P < 0.05). The median C-0 decreased from 10.7 ng/mL on the day after discontinuation of clotrimazole to 6.5 ng/mL at 1 day and 5.3 ng/mL at 2 days after its discontinuation. Conclusion Immediate dose adjustments of tacrolimus may be beneficial to avoid transplant rejection when clotrimazole troche is added or discontinued.
  • Satoshi Yokoyama; Yasuhiro Sugimoto; Chihiro Nakagawa; Kouichi Hosomi; Mitsutaka Takada
    SCIENTIFIC REPORTS 9 1 16597 - 16597 2019年11月 [査読有り]
     
    Cardiac glycosides, such as digoxin, inhibit Na+/K+-ATPases and cause secondary activation of Na+/Ca2+ exchangers. Preclinical investigations have suggested that digoxin may have anticancer properties. In order to clarify the functional mechanisms of digoxin in cancer, we performed an integrative analysis of clinical and bioinformatics databases. The US Food and Drug Administration Adverse Event Reporting System and the Japan Medical Data Center claims database were used as clinical databases to evaluate reporting odds ratios and adjusted sequence ratios, respectively. The BaseSpace Correlation Engine and Connectivity Map bioinformatics databases were used to investigate molecular pathways related to digoxin anticancer mechanisms. Clinical database analyses suggested an inverse association between digoxin and four cancers: gastric, colon, prostate and haematological malignancy. The bioinformatics database analysis suggested digoxin may exert an anticancer effect via peroxisome proliferator-activated receptor a and apoptotic caspase cascade pathways. Our integrative analysis revealed the possibility of digoxin as a drug repositioning candidate for cancers.
  • Ryosuke Ota; Atsushi Hirata; Keisuke Noto; Satoshi Yokoyama; Kouichi Hosomi; Mitsutaka Takada; Hiroshi Matsuoka
    INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS 57 11 561 - 566 2019年11月 [査読有り]
     
    Objective: We aimed to clarify the drug interaction between tacrolimus and voriconazole and investigate the relationship between blood concentrations of tacrolimus and voriconazole in hematopoietic stem cell transplantation (HSCT) patients. Materials and methods: A retrospective study was conducted to investigate the relationship between blood concentration of tacrolimus and that of voriconazole at the Kindai University Nara Hospital. Patients who received HSCT and tacrolimus and were prescribed voriconazole for the prevention or treatment of aspergillosis from April 2010 to July 2018 were identified from the medical records. A total of 13 patients (administration route of tacrolimus: intravenously in 6 patients. orally in 7 patients) were enrolled in the present study. Results: No significant correlation was observed between the blood concentration/dose (C/D) ratio of tacrolimus and the blood concentration of voriconazole (r = 0.38: p = 0.402; y = 102.8x + 928.1). However, a significant correlation was observed between the C/D ratio of tacrolimus and the blood concentration of voriconazole in the intravenous-administration group (r = 0.94; p = 0.0048; y = 421.9x + 810.5). Meanwhile, no significant correlation was observed in the oral-administration group (r = 0.43: p = 0.34; y = 7.9x + 719). Conclusion: The C/D ratio of tacrolimus was significantly correlated with the blood concentration of voriconazole when tacrolimus was intravenously administered. There was a difference in the mechanism of drug interaction between tacrolimus and voriconazole depending on the administration routes.
  • Takaya Uno; Kyoichi Wada; Sachi Matsuda; Megumi Ikura; Hiromi Takenaka; Nobue Terakawa; Akira Oita; Satoshi Yokoyama; Atsushi Kawase; Kouichi Hosomi; Mitsutaka Takada
    BRITISH JOURNAL OF CLINICAL PHARMACOLOGY 85 9 2176 - 2178 2019年09月 [査読有り]
  • Makiko Iwasawa; Keiko Sagami; Satoshi Yokoyama; Kouichi Hosomi; Mitsutaka Takada
    International journal of clinical pharmacology and therapeutics 57 4 197 - 206 2019年04月 [査読有り]
     
    OBJECTIVE: Prevalence of guideline adherence for antiulcer drug prescription in patients receiving low-dose aspirin (LDA) therapy was examined and the association of risk factors with the adherence was assessed. MATERIALS AND METHODS: A retrospective cohort study using a population-based longitudinal healthcare database was conducted. Claims data between January 2005 and April 2016 were analyzed. A total of 3,079 patients were included in the study. The selected patients taking LDA were divided into two categories: those taking and those not taking antiulcer drugs in an inpatient setting. Additionally, they were classified into four groups according to the time antiulcer therapy was initiated. The risk factors for ulcer, such as history of gastrointestinal injuries; age ≥ 65 years; and concomitant use of anticoagulants, antiplatelets, oral corticosteroids, and nonsteroidal anti-inflammatory drugs except aspirin, were assessed. RESULTS: A total of 3,079 patients were included in the study. The rate of LDA patients using antiulcer drugs was 65.2%, with the strongest single factor associated with the use of antiulcer drugs being the concomitant use of corticosteroids. Among the LDA patients not taking antiulcer drugs, 66.8% had more than one risk factor. Irrespective of the use of concomitant treatment with antiulcer drug prior to hospital admission, 78.3% of the LDA patients continued their home regimen after hospital admission. CONCLUSION: Our results showed that the requirement of antiulcer therapy is not routinely evaluated at hospital admission, and antiulcer drugs for patients with ulcer risks are under-prescribed. Developing strategies to screen gastrointestinal risk factors at hospital admission is required to improve the guideline adherence for LDA-induced ulcer.
  • Atsushi Hirata; Keisuke Noto; Ryosuke Ota; Satoshi Yokoyama; Kouichi Hosomi; Mitsutaka Takada; Hiroshi Matsuoka
    International journal of clinical pharmacology and therapeutics 57 3 135 - 143 2019年03月 [査読有り]
     
    OBJECTIVE: We aimed to investigate the relationship between voriconazole (VRCZ) trough concentrations and hepatotoxicity and to evaluate whether the recommended trough concentration is adequate in our clinical setting. MATERIALS AND METHODS: A retrospective study was performed to investigate the relationship between serum VRCZ concentrations and the development of hepatotoxicity at the Kindai University Nara Hospital. Patients treated with VRCZ from March 2010 to January 2018 were identified from the medical records. A total of 42 patients (mean age of 61.9 ± 16.9 years; 33 males and 9 females) were enrolled in this study. RESULTS: Hepatotoxicity developed in 28.6% (12/42) of patients treated with VRCZ, and 91.7% (11/12) of these patients developed hepatotoxicity within 3 weeks after initiating the treatment. Significantly increased aspartate aminotransferase (AST; p < 0.001), alkaline phosphatase (ALP; p < 0.001), and alanine aminotransferase (p = 0.001) levels were observed after the initiation of VRCZ therapy. In addition, significant positive correlations between AST and VRCZ trough concentrations (p = 0.017) and between ALP and VRCZ trough concentrations (p = 0.012) were observed. VRCZ trough concentration was identified as a significant independent risk factor for hepatotoxicity (adjusted odds ratio: 1.611, 95% confidence interval: 1.131 - 2.579, p = 0.006), and the cutoff serum trough concentration was calculated to be 4.2 μg/mL. CONCLUSION: VRCZ-induced hepatotoxicity should be noted in the early stages of therapy. A sustained VRCZ trough concentration of ~ < 4.2 μg/mL is recommended to prevent hepatotoxicity in patients with low serum albumin levels.
  • Ryo Inose; Kouichi Hosomi; Katsuyuki Takahashi; Satoshi Yokoyama; Mitsutaka Takada
    International journal of clinical pharmacology and therapeutics 57 2 63 - 72 2019年02月 [査読有り]
     
    OBJECTIVE: This study investigated whether using biological disease-modifying antirheumatic drugs (bDMARDs) further increases the risk of malignant lymphoma in patients with rheumatoid arthritis undergoing methotrexate therapy using spontaneous adverse reaction databases in different countries. MATERIALS AND METHODS: Patient data were acquired from the US Food and Drug Administration's Adverse Event Reporting System (FAERS), the Japanese Adverse Drug Event Report (JADER), and the Canada Vigilance Adverse Reaction Online Database (CVARD) from the first quarter of 2004 to the end of 2015. Data subset analysis was performed to investigate whether the use of bDMARDs further increased the risk of malignant lymphoma in patients receiving methotrexate therapy. RESULTS: The FAERS subset data indicated a significant association between Hodgkin lymphoma and methotrexate with infliximab (reporting odds ratio (ROR): 8.28. 95% CI: 5.70 - 12.02; information component (IC): 2.04, 95% CI: 1.59 - 2.49). In addition, signal scores suggested that methotrexate with infliximab (ROR: 3.26. 95% CI: 2.68 - 3.98; IC: 1.31, 95% CI: 1.04 - 1.58) was significantly associated with non-Hodgkin lymphoma (NHL). The CVARD subset data also indicated a significant association between NHL and methotrexate with infliximab (ROR: 22.82. 95% CI: 5.02 - 103.78; IC: 1.77, 95% CI: 0.13 - 3.41). However, the JADER subset data revealed no significant associations. CONCLUSION: The present study shows that using infliximab further increases the risk of malignant lymphoma in patients receiving methotrexate therapy.
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  • Takaya Uno; Kyoichi Wada; Sachi Matsuda; Yuka Terada; Nobue Terakawa; Akira Oita; Satoshi Yokoyama; Atsushi Kawase; Kouichi Hosomi; Mitsutaka Takada
    EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY 75 1 67 - 75 2019年01月 [査読有り]
     
    PurposeThis study aimed to investigate the effects of clotrimazole on the pharmacokinetics of tacrolimus in Japanese patients with heart transplants with different CYP3A5 genotypes.MethodsTwenty-six patients who underwent heart transplantation between June 2012 and July 2017 were enrolled in this retrospective study. The CYP3A5 (rs776746; CYP3A5*3) genotype was determined after monitoring and analysing tacrolimus blood concentrations. The pharmacokinetic profile of tacrolimus was examined before and after the discontinuation of clotrimazole and in patients with different CYP3A5 genotypes.ResultsThe CYP3A5*1/*1, *1/*3 and *3/*3 genotypes were detected in 2, 8 and 16 patients, respectively. After clotrimazole was discontinued, the CYP3A5 expresser (CYP3A5*1/*1 or *1/*3) group had a 3.3-fold median increase in apparent oral clearance of tacrolimus (0.27 vs. 0.89L/h/kg, P=0.002) compared with the CYP3A5 non-expresser (CYP3A5*3/*3) group with a 2.2-fold median increase (0.18 vs. 0.39L/h/kg, P<0.0001). Significant correlations were observed between C-0 and area under the concentration-time curve (AUC(0-12)) of tacrolimus after the discontinuation of clotrimazole in the CYP3A5 expresser and non-expresser groups, respectively (R-2=0.49 and 0.42, all P<0.05), but not before the discontinuation of clotrimazole.ConclusionThe effects of clotrimazole on tacrolimus pharmacokinetics in the CYP3A5 expresser patients were significantly greater than those in the CYP3A5 non-expresser patients. In addition, clotrimazole disturbed the correlation between C-0 and AUC(0-12) of tacrolimus. Careful dose adjustment of tacrolimus based on CYP3A5 genotypes may be beneficial for the patients with heart transplants who are concomitantly treated with clotrimazole.
  • Comparison of the Perception between Pharmacy Students and Practicing Pharmacists in the Acquisition of Physical Assessment Skills
    大鳥徹; 井上知美; 細見光一; ウィリアム・フィゴーニ; 北小路学; 八軒浩子; 中川博之; 高島敬子; 近藤尚美; 高田亜美; 松山賢治; 西田升三
    社会薬学 37 2 127 - 133 2018年12月 [査読有り]
  • Kouichi Hosomi; Mai Fujimoto; Kazutaka Ushio; Lili Mao; Juran Kato; Mitsutaka Takada
    PloS one 13 10 e0204648  2018年 [査読有り]
     
    Different computational approaches are employed to efficiently identify novel repositioning possibilities utilizing different sources of information and algorithms. It is critical to propose high-valued candidate-repositioning possibilities before conducting lengthy in vivo validation studies that consume significant resources. Here we report a novel multi-methodological approach to identify opportunities for drug repositioning. We performed analyses of real-world data (RWD) acquired from the United States Food and Drug Administration's Adverse Event Reporting System (FAERS) and the claims database maintained by the Japan Medical Data Center (JMDC). These analyses were followed by cross-validation through bioinformatics analyses of gene expression data. Inverse associations revealed using disproportionality analysis (DPA) and sequence symmetry analysis (SSA) were used to detect potential drug-repositioning signals. To evaluate the validity of the approach, we conducted a feasibility study to identify marketed drugs with the potential for treating inflammatory bowel disease (IBD). Primary analyses of the FAERS and JMDC claims databases identified psycholeptics such as haloperidol, diazepam, and hydroxyzine as candidates that may improve the treatment of IBD. To further investigate the mechanistic relevance between hit compounds and disease pathology, we conducted bioinformatics analyses of the associations of the gene expression profiles of these compounds with disease. We identified common biological features among genes differentially expressed with or without compound treatment as well as disease-perturbation data available from open sources, which strengthened the mechanistic rationale of our initial findings. We further identified pathways such as cytokine signaling that are influenced by these drugs. These pathways are relevant to pathologies and can serve as alternative targets of therapy. Integrative analysis of RWD such as those available from adverse-event databases, claims databases, and transcriptome analyses represent an effective approach that adds value to efficiently identifying potential novel therapeutic opportunities.
  • Satoshi Yokoyama; Yuki Tanaka; Kazuki Nakagita; Kouichi Hosomi; Mitsutaka Takada
    INTERNATIONAL JOURNAL OF MEDICAL SCIENCES 15 14 1686 - 1693 2018年 [査読有り]
     
    A historical cohort analysis of the Japan medical data center (JMDC) claims databases was performed to compare the incidence rates of bleeding events with warfarin (WF) versus direct oral anticoagulant (DOAC) treatment in patients with non-valvular atrial fibrillation. The aim of this study is to clarify the risk factors for bleeding events in younger patients newly treated with WF or DOAC in clinical practice setting. Patients who newly initiated WF or DOAC treatment from April 2012 to March 2015 were selected from the JMDC claims database. A 1:1 propensity score matching analysis was used for new users of WF or DOAC. Kaplan-Meier curves were generated to depict the time to bleeding event (total bleeding events, gastrointestinal hemorrhage, and intracranial hemorrhage) during the follow-up period. Cox proportional regression models were used to estimate the hazard ratios for total bleeding events caused by oral anticoagulants. Overall, 2,046 patients (503 WF and 1,543 DOAC) were included. After applying propensity score matching, Kaplan-Meier analysis of the WF and DOAC groups displayed comparable incidences of total bleeding events, gastrointestinal hemorrhage, and intracranial hemorrhage. Cox proportional hazards modeling showed that the use of WF was not associated with total bleeding events compared with DOAC (hazard ratio: 1.21, 95% confidence interval: 0.93-1.54, p = 0.15). This historical cohort study using a claims database indicates that the bleeding risk of DOAC was comparable to that of WF in Japanese younger population.
  • Mikie Yamato; Kyoichi Wada; Tomohiro Hayashi; Mai Fujimoto; Kouichi Hosomi; Akira Oita; Mitsutaka Takada
    CLINICAL DRUG INVESTIGATION 38 1 39 - 48 2018年01月 [査読有り]
     
    Objective This retrospective cohort study was performed to examine the association between serum amiodarone (AMD) and N-desethylamiodarone (DEA) concentrations and the development of thyroid dysfunction.Methods Patients treated with AMD from January 2012 to April 2016 were identified from the computerized hospital information system database at the National Cerebral and Cardiovascular Center. Only patients whose serum AMD and DEA concentrations had been determined at least once were included in the study.Results A total of 377 patients were enrolled. Consequently, 54 (14.3%) and 60 (15.9%) patients who developed AMD-induced thyrotoxicosis and hypothyroidism were included. The mean DEA/AMD ratio during the pre-index period in the thyrotoxicosis group (0.86 +/- 0.24) was significantly higher than in the hypothyroidism (0.68 +/- 0.27) and euthyroidism (0.78 +/- 0.30; p < 0.0001) groups. In addition, the mean DEA/AMD ratio during the post-index period in the thyrotoxicosis group (1.05 +/- 0.40) was significantly higher than in the hypothyroidism (0.81 +/- 0.24) and euthyroidism (0.88 +/- 0.22; p < 0.0001) groups. A persistently higher DEA/AMD ratio was observed throughout the study period in the thyrotoxicosis group. In addition, good correlations between the DEA/AMD ratio and the levels of free thyroxine, free triiodothyronine levels, and log (thyroid-stimulating hormone) were observed in the thyrotoxicosis and euthyroidism groups.Conclusion Patients with AMD-induced thyrotoxicosis had an increased DEA/AMD ratio and patients with AMD-induced hypothyroidism had a decreased DEA/AMD ratio before the development of thyroid dysfunction. The DEA/AMD ratio may be a predictive marker for AMD-induced thyroid dysfunction.
  • Yutaro Mukai; Kyoichi Wada; Koji Miyamoto; Kazuki Nakagita; Mai Fujimoto; Kouichi Hosomi; Takeshi Kuwahara; Mitsutaka Takada; Kengo Kusano; Akira Oita
    JOURNAL OF ARRHYTHMIA 33 5 434 - 439 2017年10月 [査読有り]
     
    Background: The periprocedural protocol for atrial fibrillation (AF) ablation commonly includes anticoagulation therapy. Apixaban, a direct oral anticoagulant, is currently approved for clinical use; however, little is known about the effects of residual apixaban concentration on bleeding complications during/after AF ablation. Therefore, we measured residual apixaban concentration by using mass spectrometry and examined the anticoagulant's residual effects on bleeding complications. Methods: Fifty-eight patients (Mean age of 64.7 +/- 12.5 years; 31 males, 27 females) were enrolled and administered apixaban twice daily. We analyzed trough apixaban concentration, activated clotting time (ACT), heparin dose, and bleeding complications during/after AF ablation. Apixaban concentrations were directly measured using mass spectrometry. Results: Bleeding complications were observed in 19 patients (delayed hemostasis at the puncture site, 16; hematuria, 3; hemosputum, 1). No patient required blood transfusion. The mean trough apixaban concentration was significantly lower in patients with bleeding complications than without (152.4 +/- 73.1 vs. 206.8 +/- 98.8 ng/mL respectively, P=0.037), while the heparin dose to achieve ACT > 300 s was significantly higher in patients with bleeding complications (9368.4 +/- 2929.0 vs. 7987.2 +/- 2135.2 U/body respectively, P=0.046). Interestingly, a negative correlation was found between the trough apixaban concentration and the heparin dose to achieve ACT > 300 s (P=0.033, R=-0.281). Conclusions: Low residual plasma apixaban is associated with a higher incidence of bleeding complications during/after AF ablation, potentially because of a greater heparin requirement during AF ablation. (C) 2017 Japanese Heart Rhythm Society. Published by Elsevier B.V.
  • Mitsutaka Takada; Mikie Yamato; Kyoichi Wada; Mai Fujimoto; Kouichi Hosomi; Tomohiro Hayashi; Akira Oita
    EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY 73 8 1053 - 1054 2017年08月 [査読有り]
  • Mai Fujimoto; Migiwa Kanou; Kouichi Hosomi; Mitsutaka Takada
    INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS 55 4 295 - 303 2017年04月 [査読有り]
     
    Objective: The aim of this study was to examine the associations between angiotensin receptor blockers (ARBs) and the risk of 10 major cancers by employing different pharmacoepidemiological assessments. Materials & methods: Data from the first quarter of 2004 through 2012 were downloaded from the US Food and Drug Administration Adverse Event Reporting System (FAERS). The reporting odds ratio (ROR) and information component (IC) were used to detect the signals. Furthermore, symmetry analysis was applied to the claims database to identify the risk of cancer after using ARBs from January 2005 to July 2013. Results: Significant inverse associations were found for all cancer types assessed as a whole (ROR: 0.78, 95% confidence interval (CI): 0.75 - 0.80; IC: -0.36, 95% CI: -0.40 to -0.31) in the analyses of FAERS database. Likewise, significant inverse association was found for all cancer types assessed as a whole (adjusted sequence ratio: 0.89, 95% CI: 0.82 - 0.96) in claims database. In addition, a significantly decreased risk for breast cancer and increased risks for pancreatic and prostate cancer were found in patients treated with ARBs in the analyses of individual cancers. Conclusions: Significant inverse association was found between ARB use and all cancer types assessed as a whole. However, in the analyses of individual cancers, the risks of ARB-induced cancer may differ according to cancer site. It may be reasonable to assume that the risks ofARB-induced cancer may differ according to cancer site.
  • Mikie Yamato; Kyoichi Wada; Mai Fujimoto; Kouichi Hosomi; Tomohiro Hayashi; Akira Oita; Mitsutaka Takada
    EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY 73 3 289 - 296 2017年03月 [査読有り]
     
    We used a retrospective data mining approach to explore the association between serum amiodarone (AMD) and N-desethylamiodarone (DEA) concentrations and thyroid-related hormone levels.Laboratory data sets from January 2012 to April 2016 were extracted from the computerized hospital information system database at the National Cerebral and Cardiovascular Center (NCVC). Data sets that contained serum AMD and DEA concentrations and thyroid function tests, including thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3), were analyzed.A total of 1831 clinical laboratory data sets from 330 patients were analyzed. Data sets were classified into five groups (euthyroidism, hyperthyroidism, subclinical hyperthyroidism, hypothyroidism, and subclinical hypothyroidism) based on the definition of thyroid function in our hospital. Most abnormal levels of thyroid hormones were observed within the therapeutic range of serum AMD and DEA concentrations. The mean DEA/AMD ratio in the hyperthyroidism group was significantly higher than that in the euthyroidism group (0.95 +/- 0.42 vs. 0.87 +/- 0.28, p = 0.0209), and the mean DEA/AMD ratio in the hypothyroidism group was significantly lower than that in the euthyroidism group (0.77 +/- 0.26 vs. 0.87 +/- 0.28, p = 0.0038). The suppressed TSH group (0.98 +/- 0.41 vs. 0.87 +/- 0.28, p < 0.001) and the elevated FT4 level group (0.90 +/- 0.33 vs. 0.84 +/- 0.27, p = 0.0037) showed significantly higher DEA/AMD ratios compared with normal level groups. The elevated TSH group showed a significantly lower DEA/AMD ratio compared with the normal group (0.81 +/- 0.25 vs. 0.87 +/- 0.28, p < 0.0001).High and low DEA/AMD ratios were associated with AMD-induced hyperthyroidism and hypothyroidism, respectively. The DEA/AMD ratio may be a predictive marker for AMD-induced thyroid dysfunction.
  • Sayoko Kinoshita; Tomohiro Hayashi; Kyoichi Wada; Mikie Yamato; Takeshi Kuwahara; Toshihisa Anzai; Mai Fujimoto; Kouichi Hosomi; Mitsutaka Takada
    JOURNAL OF ARRHYTHMIA 32 6 474 - 480 2016年12月 [査読有り]
     
    Background: Amiodarone is associated with a number of significant adverse effects, including elevated transaminase levels, pulmonary fibrosis, arrhythmia, and thyroid dysfunction. Although thyroid dysfunction is considered to be a common and potentially serious adverse effect of amiodarone therapy, the exact pathogenesis remains unknown because of its complex manifestations. Therefore, the prevalence of, and risk factors for, amiodarone-induced thyroid dysfunction in Japanese patients were investigated in the present study.Methods: A retrospective analysis of patients treated with amiodarone between January 2012 and December 2013 was performed. A total of 317 patients with euthyroidism, or subclinical hyperthyroidism or hypothyroidism, were enrolled in this study.Results: After being treated with amiodarone, 30 (9.5%) and 60 patients (18.9%) developed amiodarone-induced hyperthyroidism and amiodarone-induced hypothyroidism, respectively. Ten (33.3%) patients with amiodarone-induced hyperthyroidism and 40 (66.6%) with amiodarone-induced hypothyroidism were diagnosed within two years of the initiation of amiodarone therapy. Dilated cardiomyopathy (DCM) [Adjusted odds ratio (OR) 3.30 (95% confidence interval (CI): 1.26-8.90)1, and cardiac sarcoidosis [Adjusted OR 6.47 (95% Cl: 1.60-25.77)] were identified as predictors of amiodarone-induced hyperthyroidism. The baseline free thyroxine (T4) level [Adjusted OR 0.13 (95% Cl: 0.03-0.68)], and thyroid stimulating hormone (TSH) level [Adjusted OR1.47 (95% Cl: 1.26-1.74)] were identified as predictors of amiodarone-induced hypothyroidism.Conclusion: DCM and cardiac sarcoidosis were identified as risk factors for amiodarone-induced hyperthyroidism. Risk factors for amiodarone-induced hypothyroidism included higher baseline TSH level and lower baseline free T4 level, suggesting that subclinical hypothyroidism may be a potential risk factor for the development of amiodarone-induced hypothyroidism. (C) 2016 Japanese Heart Rhythm Society. Published by Elsevier B.V.
  • Yutaro Mukai; Kyoichi Wada; Mai Fujimoto; Kouichi Hosomi; Takeshi Kuwahara; Mitsutaka Takada
    INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS 54 10 795 - 803 2016年10月 [査読有り]
     
    Objective: The purpose of this study was to evaluate the long-term impact of therapeutic drug monitoring (TDM) services on the risk of hypoglycemia in cibenzoline therapy. In addition, we evaluated the impact of changes in clinical setting or patient background on the risk of hypoglycemia in patients receiving cibenzoline. Methods: TDM services for cibenzoline have been performed at the Japan National Cerebral and Cardiovascular Center since March 1998. A case-control study was performed from September 2012 to February 2013, and the calculated risk of hypoglycemia associated with cibenzoline use was compared with data from our previous studies, which were performed similar to 15 years ago. Results: A significantly increased risk for hypoglycemia was observed for users of cibenzoline (adjusted OR: 2.6; 95% CI: 1.5 -4.7). In an additional analysis, the calculated risk was slightly reduced (adjusted OR; 2.1, 95% CI; 1.1 -3.8) and hypertrophic obstructive cardiomyopathy (HOCM) was identified as a possible risk factor for hypoglycemia (adjusted OR: 4.7, 95% CI: 1.8 -12.3). There was a significant difference in the mean level of cibenzoline between outpatients with and without HOCM (360.5 +/- 166.9 ng/mL vs. 276.4 +/- 136.3 ng/ mL). An inverse relationship was observed between the percentage of outpatients whose cibenzoline serum level had been measured and their risk of hypoglycemia. Conclusions: Consistent TDM services for cibenzoline have contributed to a reduced risk of hypoglycemia associated with cibenzoline therapy. Patients with HOCM have a higher risk of developing hypoglycemia. Clinicians should therefore carefully monitor serum glucose levels in patients with HOCM taking cibenzoline.
  • 細見 光一
    医療薬学 42 2 87 - 97 (一社)日本医療薬学会 2016年02月 
    ナショナルデータベースを用いた抗精神病薬による錐体外路系症状のリスクについて検討した。調査期間中の抗精神病薬を含むレセプト数は医科入院外2716123940件、調剤1724339953件であった。そのうち、抗精神病薬の新親導入患者は1987525例で、男性869047例、女性1118478例であった。調剤レセプトで抗精神病薬使用患者2748497例中、医科レセプトデータと氏名IDで紐付けできた患者数は2660000例であった。抗精神病薬の新規導入患者1987525例中、抗精神病薬の処方の前後に抗パーキンソン病薬が処方された併用患者は451208例で、同時処方患者は344429例であった。非定型群と定型群が処方された併用患者は186060例で、同時処方患者は93702例であった。抗精神病薬の新規導入患者1987525例中、抗精神病薬の処方の前後に錐体外路系症状が診断された患者は402166例で、抗精神病薬の処方と同時に錐体外路系症状が診断された同時診断患者は253776例であった。
  • Mitsutaka Takada; Mai Fujimoto; Kouichi Hosomi
    INTERNATIONAL JOURNAL OF MEDICAL SCIENCES 13 11 825 - 834 2016年 [査読有り]
     
    Purpose: Some studies have suggested that the use of benzodiazepines in the elderly is associated with an increased risk of dementia. However, this association might be due to confounding by indication and reverse causation. To examine the association between benzodiazepine anxiolytic drug use and the risk of dementia, we conducted data mining of a spontaneous reporting database and a large organized database of prescriptions.Methods: Data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) from the first quarter of 2004 through the end of 2013 and data from the Canada Vigilance Adverse Reaction Online Database from the first quarter of 1965 through the end of 2013 were used for the analyses. The reporting odds ratio (ROR) and information component (IC) were calculated. In addition, prescription sequence symmetry analysis (PSSA) was performed to identify the risk of dementia after using benzodiazepine anxiolytic drugs over the period of January 2006 to May 2014.Results: Benzodiazepine use was found to be associated with dementia in analyses using the FAERS database (ROR: 1.63, 95% CI: 1.61-1.64; IC: 0.66, 95% CI: 0.65-0.67) and the Canada Vigilance Adverse Reaction Online Database (ROR: 1.88, 95% CI: 1.83-1.94; IC: 0.85, 95% CI: 0.80-0.89). ROR and IC values increased with the duration of action of benzodiazepines. In the PSSA, a significant association was found, with adjusted sequence ratios of 1.24 (1.05-1.45), 1.20 (1.06-1.37), 1.23 (1.11-1.37), 1.34 (1.23-1.47), 1.41 (1.29-1.53), and 1.44 (1.33-1.56) at intervals of 3, 6, 12, 24, 36, and 48 months, respectively. Furthermore, the additional PSSA, in which patients who initiated a new treatment with benzodiazepines and anti-dementia drugs within 12- and 24-month periods were excluded from the analysis, demonstrated significant associations of benzodiazepine use with dementia risk.Conclusion: Multi-methodological approaches using different methods, algorithms, and databases suggest that long-term use of benzodiazepines and long-acting benzodiazepines are strongly associated with an increased risk of dementia.
  • Mitsutaka Takada; Mai Fujimoto; Haruka Motomura; Kouichi Hosomi
    INTERNATIONAL JOURNAL OF MEDICAL SCIENCES 13 1 48 - 59 2016年 [査読有り]
     
    Purpose: Voltage-gated sodium channels (VGSCs) are drug targets for the treatment of epilepsy. Recently, a decreased risk of cancer associated with sodium channel-blocking antiepileptic drugs (AEDs) has become a research focus of interest. The purpose of this study was to test the hypothesis that the use of sodium channel-blocking AEDs are inversely associated with cancer, using different methodologies, algorithms, and databases.Methods: A total of 65,146,507 drug-reaction pairs from the first quarter of 2004 through the end of 2013 were downloaded from the US Food and Drug Administration Adverse Event Reporting System. The reporting odds ratio (ROR) and information component (IC) were used to detect an inverse association between AEDs and cancer. Upper limits of the 95% confidence interval (CI) of < 1 and < 0 for the ROR and IC, respectively, signified inverse associations. Furthermore, using a claims database, which contains 3 million insured persons, an event sequence symmetry analysis (ESSA) was performed to identify an inverse association between AEDs and cancer over the period of January 2005 to May 2014. The upper limit of the 95% CI of adjusted sequence ratio (ASR) < 1 signified an inverse association.Results: In the FAERS database analyses, significant inverse associations were found between sodium channel-blocking AEDs and individual cancers. In the claims database analyses, sodium channel-blocking AED use was inversely associated with diagnoses of colorectal cancer, lung cancer, gastric cancer, and hematological malignancies, with ASRs of 0.72 (95% CI: 0.60 - 0.86), 0.65 (0.51 - 0.81), 0.80 (0.65 - 0.98), and 0.50 (0.37 - 0.66), respectively. Positive associations between sodium channel-blocking AEDs and cancer were not found in the study.Conclusion: Multi-methodological approaches using different methodologies, algorithms, and databases suggest that sodium channel-blocking AED use is inversely associated with colorectal cancer, lung cancer, gastric cancer, and hematological malignancies.
  • 細見 光一; 朴 ピナウル; 豕瀬 諒; 藤本 麻依; 高田 充隆
    医薬品情報学 17 3 125 - 132 (一社)日本医薬品情報学会 2015年11月 
    日米の有害事象自発報告データベース(JADERとFAERS)を用い、錘体外路系有害事象の「発現リスク」「発現時期」「発現年齢」について検討し、次のような結果を得た。1)発現リスクは非定型抗精神病薬(以下;非定型)と定型抗精神病薬(以下;定型)の間で大差はなく、非定型においても注意が必要と考えられた。2)クロザピンは他の抗精神病薬に比べて錐体外路系有害事象が発現しにくいことが推測された。3)発現時期は、定型に比べて非定型で発現が緩徐であることが示唆され、発現を見逃されやすく症状が重篤化することが懸念された。4)発現年齢は、定型に比べて非定型で幅広い年齢層に分布していた。
  • Mitsutaka Takada; Mai Fujimoto; Migiwa Kanou; Kouichi Hosomi
    PHARMACOEPIDEMIOLOGY AND DRUG SAFETY 24 451 - 452 2015年09月 [査読有り]
  • Mai Fujimoto; Tomoya Higuchi; Kouichi Hosomi; Mitsutaka Takada
    PHARMACOEPIDEMIOLOGY AND DRUG SAFETY 24 474 - 474 2015年09月 [査読有り]
  • 細見 光一; 新居 万莉; 藤本 麻依; 高田 充隆
    医薬品情報学 17 1 15 - 20 (一社)日本医薬品情報学会 2015年05月 
    データベース、FAERSとJADERを用いて、両者から得られたニューキノロン系抗菌薬(NQs)による有害事象の安全性シグナルを比較した。解析着手時の最新データであるFAERS(2004年1Q〜2010年4Q)とJADER(2004年第一期〜2012年第三期)をそれぞれWebからダウンロードして用いた。対象としたNQsは、ノルフロキサシン(NFLX)、オフロキサシン(OFLX)、エノキサシン(ENX)、シプロフロキサシン(CPFX)、ロメフロキサシン(LFLX)、トスフロキサシン(TFLX)、スパルフロキサシン(SPFX)、レボフロキサシン(LVFX)、ガチフロキサシン(GFLX)、モキシフロキサシン(MFLX)、パズフロキサシン(PZFX)、ガレノキサシン(GRNX)、シタフロキサシン(STFX)の13種とした。有害事象は、添付文書に記載の重大な副作用のうち、抗菌薬分類においてNQsに特徴的な物を選出した。FAERSとJADERの有害事象の項目は、国際的な共通用語である医薬品規制用語集Medical Dictionary for Regulatory Activities(MedDRA)の高位グループ用語他を用いた。以上より、FAERS及びJADERを用いたNQsによる有害事象に対する解析結果を比較すると、1)両方にシグナルが認められる、2)両方にシグナルが認められない、3)FAERSのみシグナルが認められる、4)JADERのみシグナルが認められる、の4つに分類出来、FAERS及びJADER両方にシグナルが認められた事象は、過敏反応、低血糖、腱障害であり、NQsと強く関連した予防困難な有害事象である可能性を示した。
  • Mai Fujimoto; Tomoya Higuchi; Kouichi Hosomi; Mitsutaka Takada
    INTERNATIONAL JOURNAL OF MEDICAL SCIENCES 12 3 223 - 233 2015年 [査読有り]
     
    Purpose: In recent years, the potential risk of cancer associated with statin use has been a focus of much interest. However, it remains uncertain whether statin therapy is associated with cancer risk. To examine the association between statin use and the risk of cancer, we conducted data mining using the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and a large organized database of claims constructed by a database vendor (The Japan Medical Data Center Co., Ltd, Tokyo, Japan [JMDC]).Methods: Relevant reports in the FAERS, which included data from the first quarter of 2004 through the end of 2012, were identified and analyzed. The reporting odds ratio (ROR) was used to detect spontaneous report signals and was calculated using the case/non-case method. Additionally, signals were detected via the information component (IC) using the IC025 metric. Furthermore, event sequence symmetry analysis (ESSA) was applied to identify the risk of cancer following treatment with statins over the period January 2005 to July 2013.Results: In the FAERS database analyses, significant signals for colorectal cancer and pancreatic cancer were found for statins as a class. In the ESSA, significant associations between statin use and colorectal cancer and pancreatic cancer were found, with adjusted sequence ratios (95% confidence intervals) of 1.20 (1.08-1.34) and 1.31 (1.13-1.53), respectively, at an interval of 48 months.Conclusions: Multi-methodological approaches using different algorithms and databases suggest that statin use is associated with an increased risk for colorectal cancer and pancreatic cancer.
  • Mai Fujimoto; Tomoya Higuchi; Kouichi Hosomi; Mitsutaka Takada
    INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS 52 9 762 - 769 2014年09月 [査読有り]
     
    Objective: The efficacy and safety of statins have been studied in a number of clinical trials and epidemiological studies. In recent years, the Medicine and Healthcare Products Regulatory Agency (MHRA) has assessed the evidence available on the following adverse reactions associated with the use of statins: sleep disturbances, memory loss, micturition disorders (problems with urination), sexual disturbances, depression, and interstitial pneumopathy. However, the association between statin use and the risk of these adverse reactions remains unclear. To examine the association between statin use and the risk of lower urinary tract symptoms (LUTS) or the disorder causing LUTS, we carried out data mining using a prescription database. Methods: A large organized database of prescriptions constructed by a database vendor was used in the study. Symmetry analysis was used to identify the risk of LUTS after using statins over the period January 2006 to August 2013. Statin use in combination with drugs administered for storage LUTS was examined by prescription sequence symmetry analysis (PSSA). Results: A significant association between statins and drugs for storage LUTS was found, with adjusted sequence ratios (ASRs) of 1.21 (95% CI, 1.00-1.46), 1.19(95% CI, 1.04-1.38), and 1.17 (95% CI, 1.05-1.30) for intervals of 91, 182, and 365 days, respectively. In the analyses of individual statins, significant associations were found only for pravastatin. Significant associations with individual drugs for storage LUTS were found for solifenacin succinate with ASRs of 1.36 (95% CI, 1.02-1.81), 1.48 (95% CI, 1.19-1.84), and 1.47 (95% CI, 1.25-1.73) for intervals of 91, 182, and 365 days, for fiavoxate hydrochloride with an ASR of 1.56 (95% CI, 1.13-2.17) at an interval of 182 days, and for oxybutynin hydrochloride with ASRs of 2.06(95% CI, 1.11-3.94) and 1.71 (95% CI, 1.09-2.72) at intervals of 182 and 365 days. Significant associations with gender were found only in females with ASRs of 1.25(95% CI, 1.04-1.51) and 1.23(95% CI, 1.07-1.41) at intervals of 182 and 365days, respectively. Conclusions: Analysis of the prescription database showed significant association for storage LUTS in statin users.
  • Mitsutaka Takada; Mai Fujimoto; Kohei Yamazaki; Masashi Takamoto; Kouichi Hosomi
    DRUG SAFETY 37 8 653 - 653 2014年08月 [査読有り]
  • 藤本 麻依; 高本 真志; 細見 光一; 高田 充隆
    医薬品情報学 16 2 53 - 62 (一社)日本医薬品情報学会 2014年08月 
    レセプトデータを用いてスタチン系薬剤と睡眠障害について検討した。過去7年間のスタチン系薬剤新規導入者は20836人(男性11820人、平均49.4歳、女性9016人、平均54.9歳)であった。Prescription sequence symmetry analysisによる解析では、スタチン系薬剤処方前後に睡眠障害治療薬開始者は2607人で、スタチン系薬剤使用と睡眠障害治療薬の関連性は認めなかった。作用時間別睡眠障害治療薬は超短時間作用型1697人、短時間作用型1231人、中間作用型901人、長時間作用型26人で、短時間作用型ではinterval 12ヵ月でadjusted SR(調整順序比)が1.23となり、スタチン系薬剤と関連性を認めたが、他の型では認めず、脂溶性・水溶性スタチンとも睡眠障害治療薬との関連性は認めなかった。Event sequence symmetry analysisによる解析では、スタチン系薬剤新規使用者中2467人に睡眠障害名が付いていたが、スタチン系薬剤と睡眠障害の関連性は認めなかった。
  • Mitsutaka Takada; Mai Fujimoto; Kohei Yamazaki; Masashi Takamoto; Kouichi Hosomi
    DRUG SAFETY 37 6 421 - 431 2014年06月 [査読有り]
     
    Particular interest has been generated regarding the possible influence of statin use on sleep quality. However, no conclusive evidence exists that a particular statin is more likely to be associated with sleep disturbances versus others. It remains uncertain whether different statins produce different risks for sleep disturbance.To examine the association between statin use and the risk of sleep disturbances, we conducted data mining using the US Food and Drug Administration Adverse Event Reporting System (FAERS) and a large organized database of prescriptions constructed by a database vendor (Japan Medical Information Research Institute, Inc. Japan).Relevant reports in the FAERS were identified and analyzed. Data from the first quarter of 2004 through the end of 2013 were included in this study. The reporting odds ratio (ROR) was used to detect spontaneous report signals, calculated using the case/non-case method. For the ROR, a signal was detected if the lower limit of 95 % two-sided confidence interval (95 % CI) was > 1. Additionally, signal detection using the IC was conducted using the IC025 metric, a lower limit of the 95 % CI of the IC, where a signal is detected if the IC025 value exceeds 0. In addition, symmetry analysis was used to identify the risk of insomnia after using statins over the period of January 2006 to August 2013.In the analyses of the FAERS database, significant signals for sleep disturbances including disturbances in initiating and maintaining sleep, sleep disorders NEC, sleeping disorders due to a general medical condition, and parasomnias were found. In the prescription sequence symmetry analysis, a significant association between statin use and hypnotic drug use was found, with adjusted sequence ratios of 1.14 (1.03-1.26), 1.20 (1.11-1.29), and 1.18 (1.11-1.25) at intervals of 91, 182, and 365 days, respectively.Multi-methodological approaches using different algorithms and databases strongly suggest that statin use is associated with an increased risk for sleep disturbances including insomnia.
  • 豕瀬 諒; 細見 光一; 朴 ピナウル; 藤本 麻依; 高田 充隆
    医療薬学 40 5 268 - 277 (一社)日本医療薬学会 2014年05月 
    米国と日本の有害事象自発報告データベースであるFAERSとJADERを用いて、分子標的抗がん剤によるB型肝炎とC型肝炎の発現傾向、発現時期、発現年齢を解析した。FAERS、JADERともにB型肝炎とC型肝炎のシグナルが検出された薬剤はrituximabであり、rituximabによるB型肝炎発症について高い発現傾向を確認できた。rituximab投与開始から6ヵ月間、特に投与後3ヵ月前後はB型肝炎発症に最も注意すべきであり、B型肝炎の既往感染が疑われる症例にrituximabを投与する際には、50、60代を中心に幅広い年齢層でB型肝炎の発生に注意すべきと考えられた。今回、FAERSとrituximabのデータを解析し、互いに補完しあうことで海外と日本における有害事象の発現傾向の違いを把握でき、臨床現場で活用できると思われた。
  • Mai Fujimoto; Kouichi Hosomi; Mitsutaka Takada
    INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS 52 4 259 - 266 2014年04月 [査読有り]
     
    Objective: To examine the association between statin use and the risk of lower urinary tract symptoms (LUTS) in reports submitted to the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) between 2004 and 2011.Methods: Relevant reports in the FAERS were identified and analyzed. The reporting odds ratio (ROR) was used to detect spontaneous report signals, calculated using the case/non-case method. Cases were identified by the presence of reports of an adverse drug reaction (ADR) in which statins were the suspected drug. Non-cases were all the reports of the same reactions induced by drugs other than statins. The reporting odds ratio (ROR) and 95% confidential interval (CI) was calculated as a measure of disproportionality.Results: A total of 44,959,104 drug-reaction pairs was found in 2,681,739 reports. Significant RORs were found for both voiding (ROR; 1.16,95% CI; 1.10 - 1.23) and storage symptoms (ROR; 1.25, 95% CI; 1.20 - 1.30). Analysis of individual statins showed that rosuvastatin, atorvastatin, and lovastatin had significant disproportionality for voiding symptoms, while simvastatin, rosuvastatin, pravastatin, atorvastatin, pitavastatin, and lovastatin had significant disproportionality for storage symptoms. Of the four voiding symptoms, significant RORs were found for urine flow decrease and dysuria. Of the four storage symptoms, significant RORs were found for pollakiuria and nocturia. No fundamental differences in disproportionality were observed between genders.Conclusions: Analysis of the FAERS database showed small but reliable signals for LUTS in statin users. The mechanism responsible for these reactions is unknown. However, these adverse events should be monitored closely.
  • Mitsutaka Takada; Mai Fujimoto; Kouichi Hosomi
    INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS 52 3 181 - 191 2014年03月 [査読有り]
     
    Objective: Difference in the risk of gastrointestinal (GI) complications between users of enteric-coated and buffered low-dose aspirin (LDA) is unclear. The purpose of the study is to examine the difference in risk of GI damage between enteric-coated and buffered LDA products. Methods: A large and chronologically organized receipt database constructed by a database vendor was utilized. Prescription and event sequence symmetry analysis was used to identify the risk of LDA-induced GI complications over the period from January 2005 to July 2011. LDA use in combination with H2-receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) was examined by prescription sequence symmetry analysis. Likewise, symmetry analysis was undertaken to evaluate the association between the diagnosis of GI disease and the prescription of LDA products. Results: In July 2011, enteric-coated LDA users were more frequently co-administered PPIs than buffered LDA users (25.4% vs. 14.4%). Prescription sequence symmetry analysis of acid inhibitor use found no significant associations with enteric-coated LDA use and buffered LDA use. The event sequence symmetry analysis of ulcer, gastritis and duodenitis, and melena found significant associations with enteric-coated LDA use, with adjusted sequence ratios (ASRs) of 1.58 (1.23 - 2.06), 1.30 (1.03 - 1.65), and 14.38 (2.19 - 607.95), respectively, at the 6-month interval. At the 12-month interval, analysis of ulcers and melena found significant associations for enteric-coated LDA users, with ASRs of 1.39 (1.13 - 1.73) and 20.83 (3.33 - 863.25), respectively. Conclusions: Our findings do not support that there is no difference in the risk of GI complications between enteric-coated LDA and buffered LDA, but rather may imply that the risk of GI complications associated with enteric-coated LDA is higher than that with buffered LDA.
  • 細見 光一; 藤本 麻依; 八軒 浩子; 炭床 啓太; 高田 充隆
    医薬品情報学 15 4 147 - 154 (一社)日本医薬品情報学会 2014年02月 
    米国有害事象自発報告(FAERS)データベースを用いてアスピリン使用時における併用薬(抗潰瘍薬、アンジオテンシン系降圧薬、抗血栓薬)による消化管傷害への影響を確認する為に安全シグナル指標のROR、アスピリンの1日当たりの投与量、投与日数、総投与量について解析し安全性について検討した。アスピリン単独使用と比べ、H2拮抗薬併用、PPI併用、ACE阻害薬併用およびARB併用ではRORは小さく、抗凝固薬・抗血小板薬の併用ではRORが同等以上である傾向が見られた。1日当たりのアスピリン投与量は報告された86件中75〜100mgが36件と最も多かった。投与開始から傷害発現までの期間は343件中、投与日に発現が39件、1ヵ月以内が128件、1ヵ月超が215件、1年超が113件であった。総投与量は78件中1〜5gが17件と最も多かった。
  • 豕瀬諒; 細見光一; PARK Binawool; 藤本麻依; 高田充隆
    医療薬学 40 10 586 - 594 (一社)日本医療薬学会 2014年 
    関節リウマチに用いる生物学的製剤による重篤な感染症について日米の有害事象自発報告データベース(FAERS、JADER)を用いて検討した。関節リウマチに対して使用される生物学的製剤であるアバタセプト、アダリムマブ、エタネルセプト、インフリキシマブ、トシリズマブを、有害事象はB型肝炎、C型肝炎、結核、肺炎、敗血症を対象とした。全報告件数は、FAERS 29017485件、JADER 2079653件で、B型肝炎は4736件、2690件、C型肝炎は8731件、544件、結核は20070件、4588件、肺炎は239246件、56057件、敗血症は159073件、25071件であった。B型肝炎のシグナルが検出された薬剤は、FAERSではアバタセプト、エタネルセプト、インフリキシマブ、JADERではアダリムマブ、エタネルセプト、インフリキシマブであった。
  • Hiroko Hachiken; Ai Murai; Kyoichi Wada; Takeshi Kuwahara; Kouichi Hosomi; Mitsutaka Takada
    INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS 51 10 807 - 815 2013年10月 [査読有り]
     
    Objective: To provide further insights on the risks of gastrointestinal (GI) complications in individuals using low-dose aspirin (LDA), we investigated the concomitant use of LDA and antisecretory drugs. Additionally, we examined the frequency distributions of prescribing sequences for LDA and antisecretory drugs. Methods: Data from a computerized prescription order entry system was analyzed at the National Cerebral and Cardiovascular Center of Japan. LDA use in combination with H2-receptor antagonists (H2RAs) and proton pomp inhibitors (PPIs) was examined over the period from January 2001 to December 2010. Prescription sequence symmetry analyses were used to identify LDA-induced H2RAs or PPIs users. Results: In December 2010, PPIs accounted for 9.9% of the prescriptions for buffered LDA users and 16.1% of those for enteric-coated LDA users. Incident use of PPIs occurred more frequently among enteric-coated LDA users than buffered LDA users (17.6% vs. 11.0%, respectively). Prescription sequence symmetry analyses of PPI use revealed significant associations with enteric-coated LDA use, resulting in adjusted sequence ratios of 1.82 (95%CI, 1.11 - 3.03) and 1.87 (95% CI, 1.26 - 2.83) at intervals of 182 and 365 days, respectively. Enteric-coated LDA users tended to initiate PPI therapy on the same date more frequently than buffered LDA users (35.1% vs. 10.8%, respectively). Conclusions: Our findings do not support the notion that enteric-coated LDA products confer a lower risk for GI complications than buffered formulations, but may conversely imply that the risk of GI complications associated with buffered LDA is lower than that of enteric-coated LDA.
  • 大鳥 徹; 村上 悦子; 北小路 学; 細見 光一; 井上 知美; 小竹 武; 高田 充隆; 松山 賢治
    日本ファーマシューティカルコミュニケーション学会会誌 9 1 17 - 26 日本ファーマシューティカルコミュニケーション学会 2011年11月 
    薬学教育モデル・コアカリキュラムに沿った実習の実施状況を検証し、6年制長実務実習の問題点の検討と改善を目的に学生アンケートを実施した。アンケート結果は、薬学教育において改善項目の抽出などに使用されている顧客満足度(CS)分析より検討した。病院実務実習の実習内容は、「TDMについての演習あるいは実習を受けましたか?」が「要改善項目」として抽出され、薬局実務実習の実習内容は、「薬品管理に関する説明を受けましたか?」が「要改善項目」として抽出された。また、実務実習の指導にあたる指導薬剤師に関しては病院薬局共に、「指導薬剤師の言動に不快だと感じたことがありましたか?」が「改善検討項目」として抽出された。言動は実務実習を円滑に遂行する上で非常に重要かつ基本的な問題で、大学教員と実習指導薬剤師がワークショップなどで共にコミュニケーションとは何かを学び、スキルを検討する必要があった。
  • 細見 光一; 室井 延之; 東 和夫; 池田 りき子; 魚本 智子; 大川 恭子; 三宅 圭一; 中川 素子; 河本 由紀子; 清原 義史; 金 啓二; 沢崎 高志; 小野 達也; 西田 英之; 大野 真理子; 緒方 園子; 福島 昭二; 徳山 尚吾; 大西 憲明; 平井 みどり; 松山 賢治
    医療薬学 32 1 64 - 72 (一社)日本医療薬学会 2006年01月 
    無作為に選んだ兵庫県下の保険薬局31施設と病院・診療所47施設に対し,学生実習の受け入れ体制,実習内容,問題点などについてアンケート調査を行った.実習を受け入れているのは保険薬局27施設(87.1%),病院・診療所35施設(74.5%)であった.受け入れ人数は保険薬局が年に1〜5人,病院・診療所が1〜24人で,実習期間は3日〜4週間であった.実習受け入れに対するイメージと施設の規模別に関連性はなかった.実習内容は調剤と服薬指導の実施率が高く,在宅医療は実施する施設が少なかった.実習のカリキュラムは保険薬局24施設,病院・診療所31の施設で組まれていた.実習担当の薬剤師を育成していたのは保険薬局が7施設,病院・診療所が12施設であった.病院実習と薬局実習の内容の連携の必要性を多くの施設が感じていた
  • HOSOMI Kouichi; KUBO Yoshiyasu; OKUNO Akihiro; UMETANI Yoshiharu; HASHIMOTO Masaru; ARAYA Teruhisa; KOMORI Hideshi; HIRAI Midori; MATSUYAMA Kenji
    医療薬学 = Japanese journal of pharmaceutical health care and sciences 31 3 228 - 232 一般社団法人日本医療薬学会 2005年03月 
    We examined the clinical efficacy of shitei-decoction in 108 patients with hiccups with respect to various factors influencing them : sex, age, other drugs for hiccups, use of benzodiazepines, malignant tumors, use of antitumor agents, metastasis, complications and stress. Hiccups completely disappeared in 63 of the 108 patients following the administration of shitei-decoction, a rate of 58.3%. However, if we judge efficacy by the sum of patients whose hiccups disappeared and those who experienced remission, the efficacy rate for shitei-decoction was 82.4%. The chi-square test showed that there was no significant correlation between the above hiccup influencing factors and the efficacy of shitei-decoction. Despite previous reports to the contrary, there was no correlation between the efficacy of shitei-decoction and co-administration of benzodiazepines. However, the efficacy of shitei-decoction tended to be higher in patients with brain metastasis, suggesting that efficacy may be greater for central hiccups than peripheral hiccups.
  • OKUNO Akihiro; HOSOMI Kouichi; MAEKAWA Megumi; UMETANI Yoshiharu; TSUDA Yasuo; OHNISHI Shinsaku; ARAYA Teruhisa; YAMAMOTO Kinya; TAKAMIYA Shizuo; SATO Michiaki; MATSUYAMA Kenji
    医療薬学 = Japanese journal of pharmaceutical health care and sciences 30 10 656 - 665 一般社団法人日本医療薬学会 2004年10月 
    This report describes how good medication guidance may be provided to patients with blood cancer and discusses the role of the pharmacist in raising the satisfaction of patients and family members with treatment. Chemotherapy for blood cancer causes a variety of severe adverse reactions, giving patients and their families a feeling of anxiety towards it. It is therefore necessary for pharmacists to provide medication guidance in order to reduce anxiety towards drugs during long-term chemotherapy.
    In the present study, we examined questions regarding chemotherapy from patients and their families for 32 cases in the past 3 years. The 485 questions asked were classified according to subject as follows : 1) Adverse reactions-40%, 2) Chemotherapy protocol-12%, 3) Blood transfusions-7%, 4) Effects of chemotherapy-6%, 5) Granulocyte-colony stimulating factor (G-CSF) -6%, 6) Method of use-4%, 7) Drugs preventing opportunistic infections-4%, 8) Administration method-3%, 9) Chemotherapy in outpatient ward-3 %, 10) High-dose chemotherapy-3 %, 11) Discharge and short stay at home-1%, 12) Drop-out-1 %, 13) Drawing blood-1 %, 14) Color of chemotherapy agents for injection-1%, and 15) Differences between treatment strategies at other hospitals-1%.
  • Kouichi Hosomi; Akihiro Okuno; Yoshiharu Umetani; Teruhisa Araya; Kenji Matsuyama; Jun Haginaka; Masaki Mifune; Yutaka Saito
    Yakugaku Zasshi 124 9 587 - 598 2004年09月 [査読有り]
     
    We studied the color change of phenothiazines and metal-containing drugs after compound formation, followed by use of FT-Raman spectrocopy to observe any structural changes in them. When 6 phenothiazines (thioridazine hydrochloride, prochlorperazine maleate, levomepromazine maleate, chlorpromazine phenolphthalinate, fluphenazine maleate and perphenazine fendiate) formed compounds with natural aluminum silicate, the color change was accompanied by a shift of FT-Raman signals. These changes could be attributed to the structural changes of phenothiazines. This present observation can be then used in advance to avoid coloration of phenothiazines during preparative procedures with metal-containing drugs such as antacids. © 2004 The Pharmaceutical Society of Japan.
  • Kiyoharu Nishide; Ryuichi Kurosaki; Kouichi Hosomi; Hitoshi Imazato; Takehisa Inoue; Manabu Node; Toshiumi Ohmori; Kaoru Fuji
    Tetrahedron 51 40 10857 - 10866 1995年10月 [査読有り]
     
    New chiral nitroenamines 4a,b having (S)-2-t-butyldimethylsiloxymethylpyrrolidine as an auxiliary were found to be very effective for asymmetric nitroolefination of α-alkyl-γ- and δ-lactones. The enantiomeric excess of the product increased remarkably in the reaction with γ-lactones compared with previous nitroenamines 1a,b. A possible chelation model for the transition state of the asymmetric nitroolefination is discussed. © 1995 Elsevier Science Ltd.
  • Manabu Node; Ryuichi Kurosaki; Kouichi Hosomi; Takehisa Inoue; Kiyoharu Nishide; Toshiumi Ohmori; Kaoru Fuji
    Tetrahedron Letters 36 1 99 - 102 1995年01月 [査読有り]
     
    New chiral nitroenamines 4a,b were found to be very effective for asymmetric nitroolefination of α-alkyl-γ- and δ-lactones. The enantiomeric excess of the product ran up to 99 %. A possible chelation model for the transition state of the asymmetric nitroolefination was discussed. © 1994.
  • Takehisa Inoue; Kouichi Hosomi; Mamoru Araki; Kiyoharu Nishide; Manabu Node
    Tetrahedron: Asymmetry 6 1 31 - 34 1995年01月 [査読有り]
     
    σ-Symmetric bicyclic diketones 8a-c were enantioselectively reduced with baker's yeast to give the chiral hydroxy ketones 7a-c in 74-;100% ee. The reduction product (+)-7a and (-)-7′c were shown to be the chiral intermediates for the total synthesis of cantabrenonic acids derivatives 3 and hirsutene (4), respectively. The subsequent transformation of (+)-7a gave the intermediate (+)-5 for the total synthesis of capnellenols (1, 2). © 1994.

講演・口頭発表等

MISC

共同研究・競争的資金等の研究課題

  • 日本学術振興会：科学研究費助成事業
    研究期間 : 2022年04月 -2025年03月 
    代表者 : 細見 光一
  • 日本学術振興会：科学研究費助成事業
    研究期間 : 2016年04月 -2019年03月 
    代表者 : 細見 光一; 髙田 充隆; 豕瀬 涼
     
    複数のデータベース（DB）を解析し、副作用の発現傾向及びリスク因子を探索した。日本、米国、カナダなどの複数のDBを用いて、副作用を網羅的に発現傾向及びリスク因子の地域差を解析した。複数のDBの探索から、副作用の予測への活用に加え日本特有の副作用を把握できた。興味深い知見として、多剤併用に関する地域差の可能性を見い出した。また、薬剤と副作用の抑制的な関連性を見い出した。複数のDBの解析から副作用の発現傾向及ぴリスク因子の地域差をあぷり出したことは、臨床現場に寄与すると思われる。

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