横山 聡 (ヨコヤマ サトシ)

  • 薬学部 医療薬学科 准教授
Last Updated :2024/02/02

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

    レセプトデータや患者レジストリ、医薬品副作用データ等のリアルワールドデータを解析することによって、医薬品の未知の薬効探索や適正使用に貢献する研究に取り組んでいます。

研究者情報

学位

  • 博士(薬科学)

ホームページURL

J-Global ID

研究キーワード

  • 薬剤疫学   個別化医療   医薬品適正使用   医薬品情報学   

現在の研究分野(キーワード)

    レセプトデータや患者レジストリ、医薬品副作用データ等のリアルワールドデータを解析することによって、医薬品の未知の薬効探索や適正使用に貢献する研究に取り組んでいます。

研究分野

  • ライフサイエンス / 医療薬学

所属学協会

  • 日本医薬品情報学会   日本医療薬学会   日本薬学会   日本薬剤疫学会   

研究活動情報

論文

  • 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.
  • Effect of baseline urinary glucose levels on the relationship between sodium-glucose cotransporter 2 inhibitors and serum uric acid in Japanese patients with type 2 diabetes mellitus
    Tanaka Y; Ota R; Hirata A; Yokoyama S; Nakagawa C; Uno T; Hosomi K
    Pharmazie 2023年10月
  • 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.
  • Chihiro Nakagawa; Satoshi Yokoyama; Kouichi Hosomi
    The Annals of pharmacotherapy 57 6 637 - 645 2023年06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.
  • 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.
  • 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.
  • Takaya Uno; Mitsutaka Takada; Satoshi Yokoyama; Kazuyoshi Kawabata; Kouichi Hosomi
    International journal of clinical pharmacology and therapeutics 60 11 477 - 485 2022年11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.
  • Kaito Yamashiro; Mika Jouta; Kouichi Hosomi; Satoshi Yokoyama; Yuu Ozaki; Atsushi Hirata; Fumihiko Ogata; Takehiro Nakamura; Shigeharu Tanei; Naohito Kawasaki
    Scientific reports 12 1 17652 - 17652 2022年10月 
    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.
  • 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.
  • 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.
  • Takayuki Mabuchi; Kouichi Hosomi; Satoshi Yokoyama; Mitsutaka Takada
    International journal of clinical pharmacology and therapeutics 59 5 353 - 357 2021年05月 [査読有り]
     
    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.
  • Chihiro Nakagawa; Satoshi Yokoyama; Kouichi Hosomi; Mitsutaka Takada
    Therapeutic advances in musculoskeletal disease 13 1759720X211047057  2021年01月 
    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
    The 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.
  • 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 (C0) and area under the concentration-time curve of tacrolimus after discontinuation of clotrimazole (R2 = 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 C0 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.
  • 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.
  • 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.
  • Satoshi Yokoyama; Keiichi Hiramoto; Yurika Yamate
    Cutaneous and ocular toxicology 38 4 349 - 355 2019年12月 [査読有り]
     
    Purpose: We have previously reported that skin barrier function is disrupted in mice with colonic tumours induced by azoxymethane (AOM) and dextran sodium sulphate (DSS). We postulated that the impaired skin barrier function was associated with reactive oxygen species derived from gp91phox. In this study, we investigated the mechanisms underlying the impaired skin barrier function using gp91phox-/- mice. Materials and methods: We induced colonic tumorigenesis in C57BL/6j mice by AOM + DSS administration and evaluated the influence of reactive oxygen species on skin barrier function by using the hydroxyl radical scavenger N-acetyl-l-cysteine (NAC) or gp91phox-/- mice. Damage to the colon and skin following treatment with AOM + DSS was monitored using protein analysis methods and by detection of inflammatory mediators in the plasma. Results: NAC could not prevent the increase in transepidermal water loss (TEWL) and decrease in skin hydration level caused by AOM + DSS in gp91phox+/+ mice. However, gp91phox-/- mice showed no change in TEWL and skin hydration level. The dermal expression levels of nucleotide-binding domain, leucine-rich containing family, pyrin-domain containing 3 (NLRP3), and caspase-1 were reduced in gp91phox-/- mice. Moreover, the plasma concentrations of interleukin-18 and thymic stromal lymphopoietin (TSLP) were lower in gp91phox-/- mice than those in gp91phox+/+ mice. Inhibition of hydrogen peroxide production from superoxide anions in the gp91phox-/- status prevented the increased TEWL and decreased skin hydration level noted with degradation of NLRP3 and caspase-1. Conclusions: Superoxide anions may play an important role in the onset of the impaired skin barrier function in mice with colonic tumours.
  • 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 α 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]
  • Iwasawa M; Sagami K; Yokoyama S; Hosomi K; Takada M
    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.
  • 近藤有; 江尻将之; 間瀬広樹; 宮崎雅之; 荒川裕貴; 築山郁人; 佐藤由美子; 大島有美子; 小山佐知子; 牛膓沙織; 横山聡; 町支優和; 佐々木英雄; 壁谷めぐみ; 久田達也; 板倉由縁
    日本病院薬剤師会雑誌 55 3 279‐285  2019年03月
  • Hirata A; Noto K; Ota R; Yokoyama S; Hosomi K; Takada M; Matsuoka H
    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.
  • Inose R; Hosomi K; Takahashi K; Yokoyama S; Takada M
    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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  • Uno T; Wada K; Matsuda S; Terada Y; Terakawa N; Oita A; Yokoyama S; Kawase A; Hosomi K; Takada M
    European journal of clinical pharmacology 75 1 67 - 75 2019年01月 [査読有り]
     
    PURPOSE: This study aimed to investigate the effects of clotrimazole on the pharmacokinetics of tacrolimus in Japanese patients with heart transplants with different CYP3A5 genotypes. METHODS: Twenty-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. RESULTS: The 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. 0.89 L/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. 0.39 L/h/kg, P < 0.0001). Significant correlations were observed between C0 and area under the concentration-time curve (AUC0-12) of tacrolimus after the discontinuation of clotrimazole in the CYP3A5 expresser and non-expresser groups, respectively (R2 = 0.49 and 0.42, all P < 0.05), but not before the discontinuation of clotrimazole. CONCLUSION: The 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 C0 and AUC0-12 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.
  • 片山広美; 三島江津子; 佐々木俊則; 伴晶子; 横山聡; 桂川健司; 高取裕司; 宮崎雅之; 佐藤由美子; 築山郁人; 久田達也; 板倉由縁; 片山広美; 三島江津子; 佐々木俊則; 伴晶子; 横山聡; 桂川健司; 高取裕司; 宮崎雅之; 佐藤由美子; 築山郁人; 久田達也; 板倉由縁
    日本病院薬剤師会雑誌 55 1 47‐52  2019年01月
  • Yamashita S; Iguchi K; Noguchi Y; Sakai C; Yokoyama S; Ino Y; Hayashi T; Teramachi H; Sako M; Sugiyama T
    Pharmazie 74 5 286 - 289 2019年 [査読有り]
     
    Various types of fluorescent lights are found in the dispensing rooms of medical facilities, such as hospitals and pharmacies, in Japan. However, to reduce electric power consumption, it was necessary to evaluate the substitution of fluorescent lighting with light emitting diode (LED) lighting, which has become widespread in recent years. We subjectively evaluated several types of medicines stored under various light sources and found that different color changes were induced in tablets. In this study, we focused on Perlodel® tablets, containing 2.5 mg bromocriptine mesylate, as an example for the objective evaluation of the differences in the color change of tablets when stored under LED lighting and fluorescent lighting. High-performance liquid chromatography (HPLC) analysis of part of the tablet surface area revealed a change from white to light brown or dark brown after 28 days of irradiation, with a residual concentration of bromocriptine mesylate of 85.5 % under fluorescent lighting, 85.6 % under daylight-color LED lighting, 90.3 % under bulb-color LED lighting, and 99.2 % in the dark. In addition, the ultraviolet (UV)-visible spectral study of the absorbance of a photo-product at 400–550 nm indicated that the color change of the Perlodel® 2.5 mg tablet was caused by photochemical degradation of bromocriptine mesylate. Thus, this analysis of the photochemical changes in drugs stored under different light sources demonstrated the potency of LED lights. Through the objective evaluation of the color change, the cause of the color change was determined; this will allow us to develop a strategy that minimizes possible disadvantages to patients, such as a decrease in treatment efficacy owing to decomposition of the main component or adverse caused by decomposed matter.
  • Yokoyama S; Yajima S; Shimauchi A; Sakai C; Yamashita S; Noguchi Y; Ino Y; Iguchi K; Teramachi H
    Canadian Pharmacists Journal 151 6 377 - 382 2018年11月 [査読有り]
  • 政府統計データを用いた薬局に従事する薬剤師の分布に関する調査
    矢島 聖子; 島内 あかり; 堺 千紘; 横山 聡; 伊野 陽子; 松永 俊之; 寺町 ひとみ; 中村 光浩; 井口 和弘
    薬学雑誌 138 7 991 - 1000 (公社)日本薬学会 2018年07月
  • 舘知也; 野口義紘; 水井貴詞; 山下修司; 堺千紘; 横山聡; 伊野陽子; 井口和弘; 福田聖啓; 安田昌宏; 後藤千寿; 寺町ひとみ
    医療薬学 44 5 251 - 259 (一社)日本医療薬学会 2018年05月 [査読有り]
     
    2016年度第I期、第II期、第III期、2017年度第I期、第II期において、岐阜市民病院と岐阜薬科大学附属薬局の両方で実務実習を行った学生7人を対象とした。病院薬剤師25名、薬局薬剤師6名にアンケートを実施した。薬局実習が先で病院実習が後であった学生は4人、病院実習が先で薬局実習が後であった学生は3人であった。「代表的な疾患」の学修結果として、かかわった疾患については病院および薬局で8疾患はすべて網羅されていたが、服薬指導を実施した疾患については、病院および薬局で脳血管障害、精神疾患、免疫・アレルギー疾患、感染症の疾患を網羅することはできなかった。病院薬剤師および薬局薬剤師における振り返りレポートに対して、「実習施設間で実習生の実習した内容を共有するのに役に立った」で「そう思う」および「ややそう思う」と回答した割合は、病院薬剤師60%、薬局薬剤師100%であった。振り返りレポートについての意見では、前の施設での実習内容を把握することができ、指導に活かせるとの意見が多く見られたが、否定的な意見やさらなる改善点に関する意見も見られた。
  • Hiramoto K; Yamate Y; Yokoyama S
    Photodermatology, photoimmunology & photomedicine 34 3 200 - 210 2018年05月 [査読有り]
     
    BACKGROUND: Ultraviolet (UV) B irradiation has been shown to improve atopic dermatitis (AD). However, the relationship between UVB eye irradiation and AD is not known. This issue was addressed using a mouse model of AD. METHODS: The eyes of NC/Nga mice were irradiated with UVB at a dose of 1.0 kJ/m2 using a 20SE sunlamp for the duration of the experimental period. RESULTS: AD symptoms deteriorated upon UVB eye irradiation. The levels of adrenocorticotropic hormone (ACTH) in the plasma and nucleotide-binding domain and leucine-rich-containing family, pyrin domain-containing (NLRP)3 and neutrophil markers in the skin were increased in UVB-irradiated mice. Treatment with inhibitors of ACTH, caspase-1, interleukin-18, and thymic stromal lymphopoietin (TSLP) partly reversed the effects of irradiation, with the greatest improvement observed upon ACTH inhibition. The NLRP3 inflammasome was implicated in the effects of UVB irradiation. CONCLUSIONS: UVB eye irradiation causes AD symptom deterioration, which is likely mediated by ACTH and the activity of the inflammasome.
  • 薬局におけるプレアボイド事例の分析
    堺 千紘; 横山 聡; 伊野 陽子; 山下 修司; 野口 義紘; 井口 和弘; 寺町 ひとみ
    薬局薬学 10 1 201 - 207 (一社)日本薬局学会 2018年04月 [査読有り]
  • Yokoyama S; Tamaru S; Tamaki S; Nakanishi D; Mori A; Yamakawa T; Ao T; Sakata Y; Mizuno T; Iwamoto T; Watanabe K; Simomura M; Kawakami K; Konishi N; Kageyama S; Ohtani S; Yamada T; Ban S; Ooi K
    Clinical breast cancer 18 2 e157-e165 - e165 2018年04月 [査読有り]
     
    INTRODUCTION: Breast cancer patients often receive anthracycline-based chemotherapy, and chemotherapy-induced nausea and vomiting (CINV) remains one of the most uncomfortable and distressing adverse reactions. Poor control of CINV reduces the relative dose intensity of chemotherapy agents, which has been associated with poor clinical outcomes and shorter survival. The aim of the present study was to identify genetic risk factors associated with anthracycline-based CINV. PATIENTS AND METHODS: We evaluated CINV attributable to anthracycline-based chemotherapy in Japanese breast cancer patients treated with an antiemetic regimen that included palonosetron, aprepitant, and dexamethasone. Furthermore, we investigated the associations between CINV and single nucleotide polymorphisms in 6 candidate genes. RESULTS: Emesis episodes were rarely observed in the 125 patients included in the present survey (7.2%; n = 9); however, significant nausea occurred in more than one half of the patients (52.8%; n = 66). In particular, acute significant nausea was not effectively controlled. Multivariate logistic regression analysis revealed that the ABCG2 (rs2231142) AA genotype is significantly associated with acute significant nausea (odds ratio, 4.87; 95% confidence interval, 1.01-23.60; P = .049). CONCLUSION: The findings of the present study provide significant insights for developing personalized antiemetic strategies for breast cancer patients receiving anthracycline-based chemotherapy.
  • Hiramoto K; Yamate Y; Yokoyama S
    Photochemistry and photobiology 94 2 378 - 383 2018年03月 [査読有り]
     
    Atopic dermatitis (AD) is a widespread chronic skin condition that severely affects quality of life and can lead to more serious complications. Although ultraviolet (UV)A eye irradiation can exert various effects on the skin, it is unknown whether UVA can affect AD. To investigate potential associations, we used an NC/Nga mouse model of AD to study the effects of UVA eye irradiation. The eyes of mice were irradiated with a UVA dose of 100 kJ m-2 using a FL20SBLB-A lamp. Our histological data demonstrated that AD symptoms could be ameliorated by UVA eye irradiation. We also observed an increase in the levels of adrenocorticotropic hormone (ACTH), p53 and retinoid X receptor α (RXRα) in mice with UVA-irradiated eyes. In contrast, the levels of thymic stromal lymphopoietin (TSLP), period 2 (PER2) and differentiated embryo chondrocytes 1 (DEC1) protein were decreased in mice treated with UVA irradiation. Furthermore, UVA eye-irradiated mice exhibited reduced DEC1 and RXRα colocalization compared with nonirradiated mice. These results suggested that p53 and various clock gene proteins played important roles in the amelioration of AD symptoms observed after UVA eye irradiation; this technique may have therapeutic applications in AD.
  • Hiramoto K; Orita K; Yamate Y; Kasahara E; Yokoyama S; Sato EF
    The open biochemistry journal 12 87 - 102 2018年 [査読有り]
     
    Background: In modern society, irregular lifestyles are a problem. It is well known that Atopic Dermatitis (AD) occurs during physical stress in people with an irregular lifestyle. We evaluated the influence that day-and-night reversal physical stress has on AD. Methods: Six-week-old specific-pathogen-free and conventional NC/Nga male mice were used. For the day-and-night reversal procedure, the mice ran on a treadmill at a slow speed of 10 m/min for 12 h (between 8:00 and 20:00). Then, between 20:00 and 8:00, we put the mice in a dark place. This treatment was repeated every day for two weeks. The behavioral circadian rhythm of the mice was evaluated with the open field test. Then, the mice were sacrificed and histological examinations of the tissues, the expression of peptide hormones, corticosterone, Immunoglobulin E, histamine, and cytokines was performed using an enzyme-linked immunosorbent assay. Results: In the treadmill-treated conventional NC/Nga mice, AD symptoms were deteriorated compared with the non-treated conventional NC/Nga mice. The levels of Period (Per) 2, Clock, and brain and muscle arnt-like protein 1 (Bmal1) in the skin were increased constantly in the treadmill-treated conventional mice. Furthermore, the expression of Retinoic Acid-related Orphan Receptor (ROR)α, which activates Bmal1, was increased in the treadmill-treated conventional mice compared with the non-treated conventional mice. In addition, when non-treated conventional mice were administrated by the agonist of RORα, AD symptoms were deteriorated similar to treadmill-treated conventional mice. Conclusion: In the day-and-night reversal mice, the clock genes were increased constantly, indicating that this is a factor that deteriorated AD.
  • Yajima S; Shimauchi A; Sakai C; Yokoyama S; Ino Y; Matsunaga T; Teramachi H; Nakamura M; Iguchi K
    Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan 138 7 991 - 1000 2018年 [査読有り]
     
    In Japan, within the background of a progressively aging society, a community general support system is gradually being established. Under this system, community pharmacists are expected to expand their activities in local communities. Here, we surveyed the distribution of community pharmacists in Japan by using government statistics. We found that there are 153 towns/villages without community pharmacists, which is about six times the number of towns without physicians (26 towns/villages). The number of community pharmacists per 100000 population was correlated with the population of the municipality. There was a significant difference in the number of community pharmacists per 100000 population between depopulated and non-depopulated areas. A multiple regression analysis revealed that population, financial capability index, and number of physicians per 100000 population were positively associated with the number of community pharmacists per 100000 population in a given municipality. We hope that the survey provides useful information about future issues facing community pharmacy in a community general support system.
  • Yamashita S; Iguchi K; Noguchi Y; Sakai C; Yokoyama S; Ino Y; Hayashi H; Teramachi H; Sako M; Sugiyama T
    Journal of pharmaceutical health care and sciences 4 12 - 12 2018年 [査読有り]
     
    Background: In recent years, the popularity of LED lighting has rapidly increased, owing to its many advantages, including economic benefits. We examined the change in the quality of drugs during storage under LED and fluorescent lighting and found that some medicines exhibited a different degree of color change depending on the light source. The purpose of this study was to investigate the effects of different plastic storage bags on the color change over time when various medicines were stored under LED and fluorescent lighting conditions. Methods: Photostability tests were conducted on several types of target drugs. Subsequently, subjective evaluation by ten evaluators and objective evaluation by image analysis software were carried out regarding color change. Results: A similar change in color tone was observed after all types of illumination. Subjective evaluation by 10 evaluators revealed that "change in color tone" occurred in the order of bulb-color LED lighting < daylight-color LED lighting < fluorescent lighting, regardless of the type of plastic bags. A similar tendency was observed also in objective evaluation. In this study, it was considered that a brown light-shielding plastic bag was more effective than a normal plastic bag for the prevention of the color change of medicines stored under LED lighting. Conclusions: The above results suggested that the most appropriate combination of plastic bag and light source for medicine storage was a brown light-shielding plastic bag and bulb-color LED lighting.
  • Shimauchi A; Naganuma M; Sasaoka S; Hatahira H; Motooka Y; Hasegawa S; Fukuda A; Nakao S; Sakai C; Yokoyama S; Ino Y; Nakamura M; Iguchi K
    Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan 138 2 259 - 267 2018年 [査読有り]
     
    The "self-medication tax deduction" system began in Japan in January 2017, allowing people to encourage the use of OTC drugs. Package inserts contain important information for consumers regarding their use. In this study, we first checked whether the items, as required in the notifications of the Japanese Ministry of Health, Labour and Welfare, are described in the package inserts of cold remedies and analgesic antipyretics in OTC drugs. The descriptions of almost all packages checked in this study were based on the notifications, but those of a small number of them were not. Next, we examined the description of the items, unrequired in the notification, but worthy for proper use of drugs; e.g., the description of prohibition for use by "patients with severe hypertension" in case of ibuprofen-containing products, and the description was found in only seven of 180 products. Manufactures should make package inserts along with notifications, including the description for proper use of drugs.
  • 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.
  • 堺 千紘; 横山 聡; 伊野 陽子; 山下 修司; 野口 義紘; 井口 和弘; 寺町 ひとみ
    薬局薬学 = The journal of community pharmacy and pharmaceutical sciences 10 1 201 - 207 日本薬局学会 2018年 
    プレアボイド事例を共有することは薬物治療の質と安全性の向上のために有用であると考えられる。本研究では、薬局薬剤師によるプレアボイド事例を明らかにするために、2015年5月から2016年3月の間に岐阜薬科大学附属薬局において収集されたプレアボイド事例を分類し分析した。報告数は169件であり、そのうち「副作用の重篤化回避」が2件、「副作用未然回避」が68件、「薬物治療効果の向上」が99件だった。副作用未然回避報告では、「薬剤中止」が23件、「薬剤減量」が23件、「用法変更」が17件であった。同様に、薬物治療効果の向上に関する報告では、「薬剤追加」が48件、「用法変更」と「剤形変更」が15件で比較的多かった。こうしたプレアボイド事例を共有することにより、薬局薬剤師のプレアボイドへの関与向上が期待される。(著者抄録)
  • Satoshi Yokoyama; Satoko Yajima; Chihiro Sakai; Shuji Yamashita; Yoshihiro Noguchi; Yoko Ino; Kazuhiro Iguchi; Hitomi Teramachi
    Canadian Pharmacists Journal 150 6 362 - 365 2017年11月 [査読有り]
  • Yokoyama S; Hiramoto K; Yamate Y; Ooi K
    Annals of dermatology 29 4 414 - 421 2017年08月 [査読有り]
     
    BACKGROUND: Senna, one of the major stimulant laxatives, is widely used for treating constipation. Chronic senna use has been reported to be associated with colonic disorders such as melanosis coli and/or epithelial hyperplasia. However, there is no obvious information on the influence of chronic senna use on organs except for the intestine. OBJECTIVE: To clarify the influence of senna laxative use on skin barrier function by repeated senna administration. METHODS: Eight-week-old male hairless mice received senna (10 mg/kg/day) for 21 days. After administration, we evaluated transepidermal water loss (TEWL), and investigated the biomarkers in plasma and skin using protein analysis methods. RESULTS: Fecal water content on day seven was significantly increased; however, on day 21, it was significantly decreased after repeated senna administration. In the senna-administered group, TEWL was significantly higher compared to the control on days seven and 21. Plasma acetylcholine concentration and NO2-/NO3- were increased on days seven and 21, respectively. In skin, tryptase-positive mast cells and inducible nitric oxide synthase (iNOS)-positive cells were increased on days seven and 21, respectively. The increase of TEWL on days seven and 21 was suppressed by the administration of atropine and N(G)-nitro-L-arginine methyl ester, respectively. CONCLUSION: It was suggested that diarrhea or constipation induced by repeated senna administration caused the impairment of skin barrier function. There is a possibility that this impaired skin barrier function occurred due to degranulation of mast cells via cholinergic signals or oxidative stress derived from iNOS.
  • Atopic dermatitis deteriorates dextran sodium sulfate-induced ulcerative colitis via thymic stromal lymphopoietin in mice
    Hiramoto K; Orita K; Yamate Y; Yokoyama S
    J Bio Med 5 85 - 98 2017年05月 [査読有り]
  • Hiramoto K; Yokoyama S; Yamate Y
    Photodermatology, photoimmunology & photomedicine 33 2 84 - 91 2017年03月 [査読有り]
     
    BACKGROUND: We previously reported that ultraviolet (UV) A eye irradiation reduces the ulcerative colitis induced by dextran sodium sulfate (DSS). This study examined the effects of UVA on colon carcinoma induced by azoxymethane (AOM) and DSS. METHODS: We irradiated the eyes of ICR mice with UVA at a dose of 110 kJ/m2 using an FL20SBLB-A lamp for the experimental period. RESULTS: In mice treated with these drugs, the symptom of colon carcinoma was reduced by UVA eye irradiation. The levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α in the blood were increased in AOM + DSS-treated mice; however, those levels were reduced by UVA eye irradiation. The expression of β-endorphin, methionine-enkephalin (OGF), μ-opioid receptor, and opioid growth factor receptor (OGFR) of the colon was increased in the AOM + DSS-treated mice, and these levels were increased further following UVA eye irradiation. When β-endorphin inhibitor was administered, the ameliorative effect of UVA eye irradiation was reduced, and the effect of eye irradiation disappeared entirely following the administration of naltrexone (inhibitor of both opioid receptor and OGFR). CONCLUSIONS: These results suggested that UVA eye irradiation exerts major effects on AOM + DSS-induced colon carcinoma.
  • 井口 和弘; 堺 千紘; 横山 聡; 伊野 陽子; 山下 修司; 野口 義紘; 松永 俊之; 中村 光浩; 杉山 正; 寺町 ひとみ
    薬局薬学 8 2 149 - 154 (一社)日本薬局学会 2016年10月 
    医薬分業の進展やかかりつけ薬剤師の普及施策により、薬局での在庫負担は今後も増加することが予想される。各地域の薬剤師会を柱とした薬局間分割販売事業は、薬局の在庫負担の軽減において重要な位置づけにある。岐阜薬科大学附属薬局は、岐阜市薬剤師会の備蓄センター協力薬局として、薬局間分割販売業務を行っている。今回は、岐阜薬科大学附属薬局における分割販売事業の状況について現状を調べた。その結果、分割販売の実績は、地理的要因および価格的要因に規則性が観察された。また、抗生剤や後発医薬品、散剤の分割販売が多い傾向であった。本調査より、分割販売を利用する薬局に対し利便性の高い運用を考えるうえでの知見を得ることができた。(著者抄録)
  • Yokoyama S; Hiramoto K; Koyama M; Ooi K
    Cutaneous and ocular toxicology 35 3 194 - 203 2016年09月 [査読有り]
     
    CONTEXT: Alcohol is frequently used to induce chronic liver injury in laboratory animals. Alcohol causes oxidative stress in the liver and increases the expression of inflammatory mediators that cause hepatocellular damage. However, during chronic liver injury, it is unclear if/how these liver-derived factors affect distal tissues, such as the skin. OBJECTIVE: The purpose of this study was to evaluate skin barrier function during chronic liver injury. MATERIALS AND METHODS: Hairless mice were administered 5% or 10% ethanol for 8 weeks, and damages to the liver and skin were assessed using histological and protein-analysis methods, as well as by detecting inflammatory mediators in the plasma. RESULTS: After alcohol administration, the plasma concentration of the aspartate and alanine aminotransferases increased, while albumin levels decreased. In mice with alcohol-induced liver injury, transepidermal water loss was significantly increased, and skin hydration decreased concurrent with ceramide and type I collagen degradation. The plasma concentrations of [Formula: see text]/[Formula: see text] and tumor necrosis factor-alpha (TNF-α) were significantly increased in mice with induced liver injury. TNF receptor (TNFR) 2 expression was upregulated in the skin of alcohol-administered mice, while TNFR1 levels remained constant. Interestingly, the impairment of skin barrier function in mice administered with 10% ethanol was ameliorated by administering an anti-TNF-α antibody. CONCLUSIONS: We propose a novel mechanism whereby plasma TNF-α, via TNFR2 alone or with TNFR1, plays an important role in skin barrier function during chronic liver disease in these mouse models.
  • 山下 修司; 井口 和弘; 野口 義紘; 堺 千紘; 横山 聡; 伊野 陽子; 林 秀樹; 寺町 ひとみ; 酒向 孫市; 杉山 正
    医療薬学 42 7 512 - 517 (一社)日本医療薬学会 2016年07月 
    医療機関での医薬品保管における最適な照明器具の選択について検討した。対象医薬品はラシックス錠20mg、パーロデル錠2.5mg、フルイトラン錠2mg、ニポラジン錠3mg、カロナール錠200mgとした。照明は昼光色LED電球、昼白色LED電球、電球色LED電球および電球型蛍光灯を使用した。各照明器具の色温度は、それぞれ6700K、5000K、2700Kおよび5000Kである。LED照明の方が色調変化の程度が少ない傾向にある医薬品が存在した。各タイプのLED照明間の比較では、ラシックス錠20mgおよびパーロデル錠2.5mgにおいて色調変化の程度に違いが見られ、最も変化の小さかったのは電球色LED照明であった。
  • 井口 和弘; 大久保 沙知; 岩本 理央; 堺 千紘; 横山 聡; 伊野 陽子; 山下 修司; 野口 義紘; 松永 俊之; 中村 光浩; 杉山 正; 寺町 ひとみ
    日本地域薬局薬学会誌 4 1 1 - 8 日本地域薬局薬学会 2016年06月 
    著者等は以前、岐阜薬科大学附属薬局で実習を受け入れた学生の調剤ミスについて調査し、「数量間違い」が全ミスの51%を占めていたことを報告した。今回、数量間違い防止対策として、「調剤開始前に各薬剤の必要総数を計算し、調剤指示箋もしくは処方箋のコピーに記載した後、実際の調剤作業に入る」ことを定めた。その効果を検証するため、対策導入後2年間のインシデントレポートを分析し、導入前2年間と比較した。結果、処方箋枚数あたりの数量間違い発生率は導入前2.95%、導入後1.99%で有意に減少していた。
  • Yokoyama S; Hiramoto K; Koyama M; Ooi K
    Experimental dermatology 24 10 779 - 84 2015年10月 [査読有り]
     
    Dry skin has been clinically associated with visceral diseases, including liver disease, as well as for our previously reported small intestinal injury mouse model, which have abnormalities in skin barrier function. To clarify this disease-induced skin disruption, we used a dextran sulphate sodium (DSS)-induced colitis mouse model. Following treatment with DSS, damage to the colon and skin was monitored using histological and protein analysis methods as well as the detection of inflammatory mediators in the plasma. Notably, transepidermal water loss was higher, and skin hydration was lower in DSS-treated mice compared to controls. Tumor necrosis factor-alpha (TNF-α), interleukin 6 and NO2-/NO3- levels were also upregulated in the plasma, and a decrease in body weight and colon length was observed in DSS-treated mice. However, when administered TNF-α antibody or an iNOS inhibitor, no change in skin condition was observed, indicating that another signalling mechanism is utilized. Interestingly, the number of tryptase-expressing mast cells, known for their role in immune function via cholinergic signal transduction, was elevated. To evaluate the function of cholinergic signalling in this context, atropine (a muscarinic cholinoceptor antagonist) or hexamethonium (a nicotinic cholinergic ganglion-blocking agent) was administered to DSS-treated mice. Our data indicate that muscarinic acetylcholine receptors (mAChRs) are the primary receptors functioning in colon-to-skin signal transduction, as DSS-induced skin disruption was suppressed by atropine. Thus, skin disruption is likely associated with DSS-induced colitis, and the activation of mast cells via mAChRs is critical to this association.
  • Yamate Y; Hiramoto K; Yokoyama S; Ooi K
    Pharmaceutical biology 53 6 913 - 20 2015年06月 [査読有り]
     
    CONTEXT: It has been reported that chronic sennoside use is associated with the development of melanosis coli, colonic adenoma, and/or carcinomas. OBJECTIVES: In this study, we investigated the immunological changes in the colon and skin after the administration of senna. MATERIALS AND METHODS: In this study, we investigated the colon and epidermis of C57/BL6j mice after a single administration of 10 mg/kg of senna [Cassia angustifolia (Caesalpiniaceae); 3, 6, 12, and 24 h after administration] and after repeated once per week administrations (on days 3, 5, 7, 14, and 21 of administration). The LD50 and ED50 of senna used in this experiment were 165 mg/kg and 13 g/kg, respectively. RESULTS: We demonstrated that the DOPA-positive cells in the colon increased at 12 h after single administration and were further increased from at 5-28 d after repeated administration. We also studied the physiological changes of the small intestine using the charcoal meal test. We found that there was a tendency for peristalsis to be inhibited after repeated senna administration. In the epidermis, we investigated the number of Langerhans cells, because they are important immune cells of the skin. The number of these cells decreased, especially after repeated administration. DISCUSSION AND CONCLUSION: The present findings suggested that it is necessary to pay attention to not only the intestine but also the skin, during long-term senna treatment.
  • Yokoyama S; Hiramoto K; Koyama M; Ooi K
    Biological & pharmaceutical bulletin 38 6 947 - 50 2015年 [査読有り]
     
    We have previously reported that impaired skin barrier function was induced by small intestinal injury in mice. Therefore, we postulated that other intestinal diseases might also influence skin barrier function. In this study, we evaluated the skin barrier function of hairless mice with colon carcinoma that was induced by azoxymethane (AOM) and dextran sodium sulfate (DSS). In mice treated with these drugs, we observed elevated transepidermal water loss and reduced skin hydration levels, compared to those in the control mice. In addition, plasma nitrogen di/trioxide (NO2(-)/NO3(-)) levels were significantly elevated, and expression of type I collagen was significantly reduced in the treated mice, compared to those in control. These results suggest that impaired skin barrier function occurs in mice when colon carcinoma is present.
  • Yokoyama S; Hiramoto K; Koyama M; Ooi K
    Experimental dermatology 23 9 659 - 63 2014年09月 [査読有り]
     
    One mechanism by which non-steroidal anti-inflammatory drugs (NSAIDs) cause intestinal injury is by inducing matrix metalloproteinases (MMPs) that degrade and remodel the extracellular matrix. In addition to the intestinal mucosa, MMPs are expressed in the skin and can be activated by mast cell-secreted tryptase. We therefore investigated whether intestinal injury resulting from treatment with the NSAID indomethacin induced MMPs in the skin of mice and caused an associated disruption of skin function. Hairless mice and mast cell-deficient mice were administered indomethacin, after which damage to the jejuna and skin was assessed with immunohistochemistry and Western blotting. The plasma concentration of inflammatory mediators was assessed to evaluate potential pathways for signalling skin disruption in response to intestinal injury. In hairless mice with intestinal injury, transepidermal water loss (TEWL) was higher and skin hydration was lower than in control mice. The expression levels of mast cells, tryptase, MMP-1 and MMP-9 were also increased, with concurrent degradation of types I and IV collagen. In contrast, no changes in skin TEWL or skin hydration were observed in mast cell-deficient mice with indomethacin-induced intestinal injury. In all mice evaluated, the plasma concentrations of IgE, IgA, histamine and TNF-α were increased in response to indomethacin treatment. Skin disruption was strongly associated with indomethacin-induced small intestinal injury, and the activation of mast cells and induction of tryptase, MMP-1 and MMP-9 are critical to this association.
  • Skin hydrating effects of Corchorus olitorius extract in a mouse model of atopic dermatitis
    Yokoyama S; Hiramoto K; Fujikawa T; Kondo N; Konishi N; Sudo S; Iwashima M; Ooi K
    J Cosme Dermatol Sci. Appl 4 1 1 - 6 2014年04月 [査読有り]
  • Topical application of Corchorus olitorius leaf extract ameliorates atopic dermatitis in NC/Nga mice
    Yokoyama S; Hiramoto K; Fujikawa T; Kondo H; Konishi N; Sudo S; Iwashima M; Ooi K
    Dermatol Aspects 2 3  2014年02月 [査読有り]
  • 経皮吸収型鎮痛・抗炎症剤の皮膚障害性に関する研究 ロキソプロフェンナトリウムを中心として
    大井 一弥; 横山 聡; 平本 恵一
    薬理と治療 42 2 107 - 113 ライフサイエンス出版(株) 2014年02月 
    経皮吸収型鎮痛・抗炎症剤の皮膚障害性について、マウスを用いて24時間貼付後の変化を調べた。試験薬剤はサージカルテープ優肌絆スキンカラー、高含水シート、ロキソニンテープおよびパップ、ロキソプロフェンナトリウムテープおよびパップ、モーラステープの7剤とした。貼付剤除去1時間後および24時間後の皮膚反応はモーラステープ以外は認めず、掻爬の回数は1時間後で対照群(脱脂綿固定)に比較して各試験薬剤で有意に増加したが、モーラステープで最も高値であった。経表皮水分喪失はスキンカラー以外のテープ剤は対照群より高値で、ロキソニンテープ剤の製剤間に差はなかった。角質水分量は除去1時間にモーラステープで有意な減少を認めた。角質剥離量は、パップ剤に比較してテープ剤が高値であった。表皮の肥厚は、組織学的検討でテープ剤の除去1時間後に認めた。サブスタンスPの発現増加はモーラステープでのみ認めた。
  • 大井 一弥; 横山 聡; 阿波 勇樹; 河井 亜希; 平本 恵一
    西日本皮膚科 76 2 127 - 130 日本皮膚科学会-西部支部 2014年 
    タクロリムス軟膏とヘパリン類似物質製剤の塗布順序によるタクロリムスの皮膚内移行性について,アトピー性皮膚炎モデル動物であるNOA/Jclマウスにより検討を行った。NOA/Jclマウスの背部にタクロリムス軟膏を塗布し,タクロリムス軟膏(プロトピック軟膏0.1%)およびヘパリン類似物質製剤(ヒルドイドソフト軟膏0.3%,ヒルドイドクリーム0.3%,ヒルドイドローション0.3%)塗布後,3時間の皮膚中タクロリムス濃度をLC-MS/MSを用いて測定した。タクロリムス軟膏塗布後,ヒルドイドソフト軟膏塗布はA群,ヒルドイドソフト軟膏塗布後,タクロリムス軟膏塗布はB群,タクロリムス軟膏塗布後,ヒルドイドクリーム塗布はC群,ヒルドイドクリーム塗布後,タクロリムス軟膏塗布はD群,タクロリムス軟膏塗布後,ヒルドイドローション塗布はE群,ヒルドイドローション塗布後,タクロリムス軟膏塗布はF群,タクロリムス軟膏とヒルドイドソフト軟膏混合塗布はG群とした。この結果,タクロリムス軟膏とヘパリン類似物質製剤の塗布順序の違いによる皮膚中タクロリムス濃度に,有意な差はなかった(P=0.8325)。また,タクロリムス軟膏と各剤形のヘパリン類似物質製剤の塗布順序による皮膚中タクロリムス濃度についても検討したところ,有意な差はなかった(P=0.0811)。さらに,タクロリムス軟膏とヘパリン類似物質製剤の混合塗布した場合とタクロリムス軟膏とヘパリン類似物質製剤の各々の塗布順序でも有意差は認められなかった(A群との比較:P=0.0958,B群との比較:P=0.1331)。これらのことから,タクロリムス軟膏とヘパリン類似物質製剤の塗布順序の違いが,皮膚中タクロリムス濃度に影響を与える可能性は低いと考えられる。従って,臨床ではどちらを先行塗布しても効果に差を認めるものではないことが推察される。(著者抄録)
  • パクリタキセル注射液「NP」のマウス白血病L1210細胞に対する抗腫瘍効果
    大井 一弥; 横山 聡; 河井 亜希; 阿波 勇樹; 平本 恵一
    薬理と治療 41 6 573 - 576 ライフサイエンス出版(株) 2013年06月 
    L1210細胞をマウスの腹腔内に移植し、パクリタキセル注射液「NP」とタキソール注射液(いずれもパクリタキセルとして6および12mg/kg/day)または媒体を移植後5日間腹腔内投与し、移植28日後まで生死の確認および体重測定を実施した。媒体対照群は8日目までに全例が死亡し、平均生存日数は7.3日であった。パクリタキセル6mg/kg/dayにおける平均生存日数と延命率は「NP」が8.8日および20.5%、タキソールが9.4日および28.8%であり、パクリタキセル12mg/kg/dayにおける平均生存日数と延命率はNP」が10.9日および49.3%、タキソールが9.5日および30.1%であった。媒体対照群と比較していずれの製剤においても有意な延命を認め、同一用量において製剤間に有意差は認めなかった。「NP」の抗腫瘍作用はタキソールと同等の有効性を示すと考えられた。
  • Mild exercise suppresses exacerbation of dermatitis in NC/Nga mice: correlation with β-endorphin Levels
    Hiramoto K; Sato EF; Kobayashi H; Yokoyama S; Ooi K
    J Clin Exp Dermatol Res 4 180  2013年03月 [査読有り]
  • シスプラチン投与時の制吐療法におけるパロノセトロンとアプレピタントの効果
    横山 聡; 藪田 ゆみ; 埋橋 賢吾; 坂 晋; 大田 博子; 藤川 隆彦; 大井 一弥
    薬理と治療 40 12 1073 - 1078 ライフサイエンス出版(株) 2012年12月 
    シスプラチンを含む高度催吐性化学療法を受けた患者を対象として、GD(グラニセトロン+デキサメタゾン)レジメン、GAD(グラニセトロン+アプレピタント+デキサメタゾン)レジメンおよびPAD(パロノセトロン+アプレピタント+デキサメタゾン)レジメンの悪心・嘔吐抑制効果を後方視的に比較検討し、制吐レジメンにおけるパロノセトロンおよびアプレピタントの有効性を検討した。GAD群ならびにPAD群の全期間CR率はそれぞれ83.8%、82.9%で、GD群の55.3%に比して有意に高くなった。PAD群の全期間「有意な悪心なし」の割合は80.0%で、GD群の29.8%に対して有意に高値を示した。女性におけるCR率はGD群よりもGAD群やPAD群のほうが有意に高かった。男性におけるPAD群の「有意な悪心なし」の割合は、GD群とくらべて有意に高値を示し、女性におけるPAD群では、GD群やGAD群と比べて有意に高値を示した。
  • The optimal conditions for use of the hydration patch, Win Back®, on human skin
    Kazuya Ooi; Satoshi Yokoyama; Masahiko Hayashi; Takahiko Fujikawa; Norihiro Shinkai; Noriko Nakagima; Hitoshi Yamauchi
    Jpn Pharmacol Ther 40 11 1005 - 1010 2012年11月 [査読有り]
  • 林 雅彦; 西村 嘉洋; 横山 聡; 垣東 英史; 大井 一弥
    医療薬学 38 6 339 - 349 (一社)日本医療薬学会 2012年06月 
    模擬体験型のバイタルサイン実習を組み込んだ早期体験学習を1年次前期に行った。バイタルサイン教育を取り入れた早期体験学習の教育効果を評価する目的でアンケート調査を実施した。また、改善項目抽出のための統計処理方法として用いられている顧客満足度(CS)分析を用いて、早期体験学習における改善項目の抽出を試みた。最優先で取り組むべき項目は、「医療人としての自覚を培う必要性を理解できる」そして「薬剤師の仕事にやりがいを感じる」であることが、事前アンケートのCS分析から明らかとなった。次に取り組むべき課題は、「患者を治したい気持ちになること」、「卒業後のイメージを形成すること」であった。早期体験学習後に卒業後の希望職種を調査した結果では、25.3%の学生が卒業後の進路を明確に示さなかった。
  • Yokoyama S; Kouyama M; Kuratsune M; Imamura Y; Nakamitsu A; Fukuda Y; Ohta H
    Gan to kagaku ryoho. Cancer & chemotherapy 39 5 817 - 20 2012年05月 [査読有り]
     
    A 59-year-old male with chronic kidney disease was diagnosed as having advanced gastric cancer(cT2N1P0H1M0), and CPT-11+CDDP therapy was started for him simultaneously with hemodialysis(HD). Serum CDDP concentrations were measured in the 1st course, and free-platinum(f-Pt)showing the anti-tumor effect was found to be eliminated by HD. Serum f-Pt levels, however, re-elevated until 24 hours after HD completion. Serum concentrations measured in the 15th course showed that f-Pt levels became higher than those observed in the 1st course, suggesting that CDDP was not completely removed by HD. Medical treatment was continued until the liver metastases were judged to be a progression disease at completion of the 18th course. When CDDP was administered to patients on HD, it was necessary to pay attention to various CDDP serum concentrations, and to tailor the dose to a tolerable level in each patient. Such an individual therapy might enable CPT-11+CDDP therapy to be one of the medical treatments of choice for advanced gastric cancer patients on HD.
  • Uegami S; Imamura Y; Daimaru Y; Nakamitsu A; Kouyama M; Kuwada A; Toge K; Taogoshi H; Yokoyama S; Fukuda Y
    Gan to kagaku ryoho. Cancer & chemotherapy 38 2 321 - 4 2011年02月 [査読有り]
     
    A 73-year-old man was referred to our hospital with sigmoid colon cancer in July 2009. CT and MRI showed synchronous multiple liver metastasis. After a sigmoid colon resection in August, he received convergent chemotherapy in combination with 5-fluorouracil(5-FU)/Leucovorin(LV)(RPMI regimen)and bevacizumab for liver metastasis. After two courses without any major adverse effects, liver metastasis remarkably reduced on CT and MRI examination. We thus performed a liver resection, and pathological examination revealed a complete response in liver. Combination chemotherapy of 5-FU/LV and bevacizumab can be expected to provide safe and effective treatment for liver metastasis of colon cancer.
  • イリノテカン塩酸塩によるコリン様症状の発現状況とその対策
    横山 聡; 野村昌代; 只佐正嗣; 桒田亜希; 今村祐司; 安本壽枝; 大田博子
    日本病院薬剤師会雑誌 46 2 223 - 226 2010年02月 [査読有り]
  • Yokoyama S; Imamura Y; Hatano N; Fukuoka T; Usui H; Morita Y
    Gan to kagaku ryoho. Cancer & chemotherapy 36 7 1159 - 61 2009年07月 [査読有り]
     
    Severe neutropenia attributable to irinotecan hydrochloride (CPT-11) is reportedly associated with gene polymorphism of UGT1A1 related to its metabolism. Case 1 is a 70-year-old male patient with rectal cancer that had spread to the liver. Although he received six courses of mFOLFOX6, his hepatic metastasis recurred. Therefore, the regimen was switched to FOLFIRI. The CPT-11 dosage was 150 mg/m(2). Twelve days after the first course was attempted, neutropenia at grade 4 and a fever of 39 degrees C were found. Case 2 is a 65-year-old male whose sigmoid colon cancer had spread to the liver. We started FOLFIRI with a CPT-11 dosage of 120 mg/m(2). Nine days following administration of the first course, we found neutropenia of grade 3 and a fever of 38 degrees C. Analysis of the UGT1A1 gene polymorphism after symptom improvement revealed UGT1A1(*)28 homozygosity in both cases, which suggests that when FOLFIRI is conducted on a patient with homozygous UGT1A1(*)28, it is necessary to pay attention to neutropenia even with a CPT-11 dosage of 120 mg/m(2).
  • Suzuki K; Yokoyama S; Waseda S; Kodama S; Watanabe M
    Cancer Research 63 5 936 - 41 2003年03月 [査読有り]
     
    Ionizing radiation induces genomic instability, which is transmitted through many generations after irradiation in the progeny of surviving cells. To detect delayed activation of p53, we constructed a reporter plasmid containing the p53-responsible promoter and the bacterial beta-galactosidase (beta-gal) gene and introduced it into human fibrosarcoma (HT1080) cells, which retain wild-type p53 function. The resultant clones induce beta-gal protein after X-irradiation, and the induction kinetics were similar to those of p21(WAF1/CIP1) protein. More than 90% of the cells were stained blue when the cells were incubated with X-gal 4 h after 6 Gy of X-rays, whereas very few control cells were beta-gal positive. The primary colonies formed after 6 Gy of X-rays were collected, and they were subjected to secondary colony formation. We observed that a significant number of surviving colonies contained beta-gal-positive cells, suggesting that delayed activation of p53 occurred in the progeny of irradiated cells. We also found higher frequency of phosphorylation of p53, NBS1, and CHK2/Cds1 in the progeny of surviving cells. Furthermore, foci formation of phosphorylated histone H2AX was detected in the progeny of surviving cells. These findings provide the possibility that the observed instability results from these DNA breaks, i.e., the breaks lead to delayed chromosome rearrangements, delayed cell death, and so forth, many generations after irradiation and that activation of p53 function may eliminate cells that have potentially accumulated genomic alterations.

書籍

講演・口頭発表等

  • 米国有害事象自発報告(FAERS)を用いた、免疫抑制剤による発癌リスクに関する研究
    宇野 貴哉; 細見 光一; 和田 恭一; 横山 聡; 小田 亮介; 服部 雄司; 老田 章; 高田 充隆
    日本薬学会年会要旨集 2020年03月 (公社)日本薬学会
  • 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 2020年03月 (公社)日本薬学会
  • Fenofibrate投与に伴う急性腎不全、横紋筋融解症に対するsimvastatin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 2020年03月 (公社)日本薬学会
  • 米国有害事象自発報告(FAERS)を用いた、免疫抑制剤による発癌リスクに関する研究
    宇野 貴哉; 細見 光一; 和田 恭一; 横山 聡; 小田 亮介; 服部 雄司; 老田 章; 高田 充隆
    日本薬学会年会要旨集 2020年03月 (公社)日本薬学会
  • Fenofibrate投与に伴う急性腎不全、横紋筋融解症に対するsimvastatin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 2020年03月 (公社)日本薬学会
  • Inverse association between digoxin and cancers derived from real world data  [通常講演]
    Yokoyama, Satoshi; Sugimoto, Yasuhiro; Nakagawa, Chihiro; Hosomi, Kouichi; Takada, Mitsutaka
    PHARMACOEPIDEMIOLOGY AND DRUG SAFETY 2019年08月 WILEY
  • 竹内健人; 竹内健人; 森章哉; 森章哉; 土本大輔; 土本大輔; 福岡智宏; 福岡智宏; 池田義明; 池田義明; 横山聡; 横山聡; 福井愛子; 福井愛子; 宮澤憲治; 宮澤憲治; 山川卓哉
    日本臨床腫瘍薬学会学術大会講演要旨集 2018年
  • 改訂モデル・コアカリキュラムに基づく実務実習トライアルについての岐阜薬科大学附属薬局の取り組み  [通常講演]
    寺町 ひとみ; 野口 義紘; 舘 知也; 伊野 陽子; 山下 修司; 堺 千紘; 横山 聡; 井口 和弘
    日本薬剤師会学術大会講演要旨集 2017年10月
  • 玉木 慎也; 渡邊 健一; 田丸 智巳; 水野 聡朗; 岩本 卓也; 中西 大介; 下村 誠; 森 章哉; 川上 恵基; 山川 智一; 小西 尚巳; 青 孝明; 影山 慎一; 阪田 安彦; 大谷 彰一郎; 山田 知美; 横山 聡; 坂 晋; 大井 一弥
    日本乳癌学会総会プログラム抄録集 2017年07月
  • 難消化性デキストリン継続摂取の肥満に関する指標への影響  [通常講演]
    矢島 聖子; 井口 和弘; 葛城 大介; 松永 俊之; 宮崎 孝; 堺 千紘; 横山 聡; 伊野 陽子; 寺町 ひとみ
    日本地域薬局薬学会誌 2017年07月
  • 処方箋への検査値表示と薬局薬剤師の役割 岐阜薬科大学附属薬局の取り組み  [通常講演]
    寺町 ひとみ; 堺 千紘; 野口 義紘; 山下 修司; 横山 聡; 伊野 陽子; 井口 和弘
    日本地域薬局薬学会誌 2017年07月
  • かかりつけ薬局・薬剤師のための研修会の実施とその評価  [通常講演]
    伊野 陽子; 舘 知也; 堺 千紘; 大久保 沙知; 山下 修司; 野口 義紘; 横山 聡; 井口 和弘; 寺町 ひとみ
    日本薬学会年会要旨集 2017年03月
  • 岐阜薬科大学附属薬局の薬学部教員を対象とした在宅医療に関する研修の効果  [通常講演]
    横山 聡; 小林 篤史; 渡辺 康介; 井口 和弘; 山下 修司; 堺 千紘; 野口 義紘; 伊野 陽子; 山脇 正永; 寺町 ひとみ
    日本薬学会年会要旨集 2017年03月
  • LED照明下での保管における医薬品の品質変化と対応策の検討  [通常講演]
    山下 修司; 井口 和弘; 野口 義紘; 堺 千紘; 横山 聡; 伊野 陽子; 林 秀樹; 寺町 ひとみ; 酒向 孫市; 杉山 正
    日本薬剤師会学術大会講演要旨集 2016年10月
  • ビソプロロール貼付による皮膚障害性に関する研究  [通常講演]
    大井 一弥; 横山 聡; 小川 文歌; 平本 恵一
    日本薬学会年会要旨集 2015年03月
  • DSS腸炎マウスにおけるアセチルコリン受容体を介した皮膚障害の発現  [通常講演]
    横山 聡; 平本 恵一; 小山 真由; 大井 一弥
    日本薬学会年会要旨集 2015年03月
  • センノサイド投与マウスにおける脳・皮膚・腸の相互関係  [通常講演]
    平本 恵一; 山手 百合香; 横山 聡; 大井 一弥
    日本薬剤学会年会講演要旨集 2014年05月
  • モロヘイヤ抽出物のアトピー性皮膚炎モデルマウスにおける保湿効果  [通常講演]
    横山 聡; 平本 恵一; 藤川 隆彦; 近藤 宏哉; 小西 信幸; 須藤 秀; 岩島 誠; 大井 一弥
    日本薬剤学会年会講演要旨集 2014年05月
  • タクロリムス軟膏とヘパリン類似物質製剤併用時の塗布順序に関する研究  [通常講演]
    大井 一弥; 横山 聡; 平本 恵一
    日本皮膚科学会雑誌 2014年04月
  • 雄幼若期ラットにおける有機フッ素化合物N-EtFOSE曝露による血清テストステロン濃度変化  [通常講演]
    坂 晋; 松岡 道美; 横山 聡; 黒田 祐; 里見 佳子; 原田 均; 井上 純子; 大西 志保; 川西 正祐
    日本薬学会年会要旨集 2014年03月
  • Crush syndromeにおける腎障害に対するオルメサルタンメドキソミルの影響に関する研究  [通常講演]
    河井 亜希; 阿波 勇樹; 小川 文歌; 小山 真由; 横山 聡; 平本 恵一; 大井 一弥
    日本腎臓病薬物療法学会誌 2013年09月
  • 有機フッ素化合物N-EtFOSE胎児期曝露による雌雄胎仔の胎盤遺伝子発現量変化  [通常講演]
    坂 晋; 松岡 道美; 横山 聡; 里見 佳子; 原田 均; 井上 純子; 大西 志保; 川西 正祐
    日本薬学会年会要旨集 2013年03月
  • 外来化学療法の現状とあり方 地域がん診療連携拠点病院において薬剤部が担う役割とは  [通常講演]
    中島 恵子; 礒貝 明彦; 井向 幹栄; 小川 智恵子; 只佐 正嗣; 藤堂 未来; 横山 聡; 大田 博子; 福田 康彦
    日本農村医学会雑誌 2009年09月
  • 抗がん剤(塩酸イリノテカン)による重篤な副作用回避を目的とした遺伝子多型解析法の検討  [通常講演]
    横山 聡; 福岡 達仁; 碓井 裕史; 森田 保司
    日本農村医学会雑誌 2008年09月
  • 遺伝子検査を併用した禁煙支援のあり方に関する研究  [通常講演]
    久保 知子; 川村 洋子; 野村 恵美; 鎌田 恭子; 碓井 裕史; 福岡 達仁; 横山 聡
    日本禁煙学会学術総会プログラム・抄録集 2008年08月
  • 薬物治療モニタリング(TDM)による抗MRSA薬の適正使用への取り組み  [通常講演]
    前田 奈穂; 知念 聖子; 胡 由希子; 角井 碧; 正畠 和美; 横山 聡; 大田 博子; 森田 保司
    日本農村医学会雑誌 2008年07月
  • 消化器癌治療のキードラッグである塩酸イリノテカンの重篤な副作用回避を目的とした遺伝子検査法  [通常講演]
    横山 聡; 森田 保司; 福岡 達仁; 碓井 裕史
    日本農村医学会雑誌 2007年07月
  • 遺伝子検査を併用した個別禁煙支援  [通常講演]
    碓井 裕史; 鎌田 恭子; 野村 恵美; 久保 知子; 福岡 達仁; 横山 聡
    共済エグザミナー通信 2007年01月 
    広島市周辺の農協関連職員の喫煙者を対象とし、あらかじめ健康に対する喫煙の害、遺伝子検査を併用した禁煙支援を行う旨の文書を配布した。その後、事業所に医師、保健師が出向き、説明会を開催した。事業所の定期健診受診者は318例で、喫煙者は92例であった。これらのうち遺伝子検査を希望する者は46例で、すべて男性であった。禁煙プログラムを開始した11例中4例が、遺伝子検査の結果が禁煙のきっかけになったと回答した。ニコチン代替療法としてニコチンガムを無償で供与し、禁煙指導を行った11例中7例が使用した。禁煙指導グループで喫煙を再開した8例中3例は喫煙本数が減った。回答のあった44例中15例が行動変容を示し、禁煙あるいは節煙を行った。現在まで禁煙プログラム参加の3例が禁煙を継続している。
  • 遺伝子検査を併用した個別禁煙支援  [通常講演]
    碓井 裕史; 鎌田 恭子; 野村 恵美; 久保 知子; 福岡 達仁; 横山 聡
    日本農村医学会雑誌 2006年09月

MISC

受賞

  • 2023年10月 日本薬学会関西支部 第73回日本薬学会関西支部総会・大会:優秀口頭発表賞
     2 型糖尿病患者における sodium-glucose cotransporter 2 阻害薬と膵がんとの関連性―大規模レセプトデータを用いた解析― 
    受賞者: 田中侑希;横山聡;宇野貴哉;細見光一
  • 2023年06月 日本医療薬学会 第5回フレッシャーズ・カンファランス:優秀演題発表賞
     てんかん患者を対象とした,抗てんかん薬の併用療法とSJS/TENの関連性の調査 
    受賞者: 西杏奈;中川千拓;宇野貴哉;横山聡;細見光一
  • 2023年03月 日本薬学会 日本薬学会第143年会:学生優秀発表賞
     経口抗凝固薬使用患者における出血とポリファーマシーの関連:レセプトデータを用いた後ろ向きコホート研究 
    受賞者: 岩崎翠月;中川千拓;横山聡;細見光一
  • 2022年06月 日本医療薬学会 第5回フレッシャーズ・カンファランス:優秀演題発表賞
     非弁膜症性心房細動患者における経口抗凝固薬とがん発症の関連性の検討 
    受賞者: 山本健太,中川千拓,横山聡,細見光一
  • 2022年04月 日本薬学会 日本薬学会第142年会:学生優秀発表賞
     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 
    受賞者: 田中侑希,横山聡,細見光一
  • 2021年10月 日本薬学会関西支部 第71回日本薬学会関西支部総会・大会:優秀口頭発表賞
     抗精神病薬と関節リウマチの関連性の検討―リアルワールドデータを活用したドラッグリポジショニング― 
    受賞者: 中川千拓,横山聡,細見光一
  • 2021年04月 日本薬学会 日本薬学会第141年会:学生優秀発表賞(ポスター発表の部)
     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 
    受賞者: 小松唯可,細見光一,横山聡,髙田充隆
  • 2008年11月 日本農村医学会 第57回日本農村医学会学術総会:最優秀演題賞
     抗がん剤(塩酸イリノテカン)による重篤な副作用回避を目的とした遺伝子多型解析法の検討 
    受賞者: 横山聡,福岡達仁,碓井裕史,森田保司

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 若手研究
    研究期間 : 2023年04月 -2028年03月 
    代表者 : 横山 聡
  • 日本学術振興会:科学研究費助成事業 若手研究
    研究期間 : 2019年04月 -2023年03月 
    代表者 : 横山 聡
     
    新薬の開発には10年以上という長い期間と莫大な資金が必要であるにもかかわらず,成功率は極めて低く,近年は新薬の創出が困難になっている。このような背景の中,ドラッグ・リポジショニングが注目されている。本研究では,リアルワールドデータの1つであるレセプトデータベースを中心として,有害事象自発報告データベースやバイオインフォマティクス関連データベースを統合解析することでドラッグ・リポジショニング候補薬剤の戦略的なスクリーニング法の基盤構築を目的とする。2019年度は悪性腫瘍に対するドラッグ・リポジショニング研究として,リアルワールドデータとトランスクリプトームデータベースを統合解析することによってジゴキシンの抗腫瘍効果の可能性について論文で報告した。また,超高齢社会で問題となる骨粗鬆症をターゲットとして,骨粗鬆症と抗精神病薬や経口抗凝固薬との関連性について検討を行った。薬剤性の骨粗鬆症が懸念されている中で,発症リスクを低減させる医薬品の探索を行っており,2020年度にこれらの結果の一部を論文で報告した。2021年度の大きな成果としては,難治性疾患の1つである関節リウマチに対する候補薬剤の同定に成功し,論文発表を行った。現在は,アミオダロンによって誘発される甲状腺機能障害の発症予防に有用な薬剤のスクリーニングも試みており,まずは,併用薬剤数が増えることで薬物相互作用の影響を受けて甲状腺機能障害の発症リスクが増大する可能性について論文で報告した。同様に,オキサリプラチンによって誘発される末梢神経障害の発症予防あるいは治療に有用な薬剤のスクリーニングを試みており,既に末梢神経障害の発現プロファイルを明らかにして論文報告をした。

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