1 0 0 0 OA PK/PDモデリングの実際
- 著者
- 松本 宜明 清水 万紀子 福岡 正道
- 出版者
- The Japanese Society for the Study of Xenobiotics
- 雑誌
- 薬物動態 (ISSN:09161139)
- 巻号頁・発行日
- vol.15, no.5, pp.452-460, 2000 (Released:2007-03-29)
- 参考文献数
- 42
Recently, an increasing number of pharmaceutical scientists and clinical pharmacists have begun to focus on pharmacodynamics, which relates the time course of drug concentration to the time course of pharmacological effects. An integration knowledge of pharmacokinetics and pharmacodynamics is essential for the development of rational pharmacotherapeutics because pharmacodynamics and pharmacokinetics are able to determines the drug concentration required to produce the desired therapeutic effect and the drug dose regimen required to achieve the targeted drug concentration, respectively, by using various models. The general principles of the drug effect model are based on the reversible direct and indirect models. In this review, various models in terms of the time course of drug effects are presented and discussed.
1 0 0 0 OA CHDF施行患者におけるミカファンギン体内動態に関する検討
- 著者
- 清水 万紀子
- 出版者
- 公益社団法人 日本薬学会
- 雑誌
- YAKUGAKU ZASSHI (ISSN:00316903)
- 巻号頁・発行日
- vol.129, no.11, pp.1351-1356, 2009 (Released:2009-11-01)
- 参考文献数
- 23
- 被引用文献数
- 1 2
Individual differences of drug-metabolizing enzymes are important determinants for the metabolic fate of chemicals. This article focuses on polymorphic human flavin-containing monooxygenase 3 (FMO3) and dietary-derived trimethylamine. Malodorous trimethylamine is generally converted to odorless trimethylamine N-oxide by liver microsomal FMO3. Trimethylaminuria is caused by functional disorder of FMO3. In this study mutations of the FMO3 gene were examined in self-reported Japanese trimethylaminuria subjects that showed low FMO3 metabolic capacity in urine tests. Nine novel polymorphisms in the FMO3 gene were discovered in self-reported Japanese volunteers. Functional analyses of recombinant FMO3 proteins suggested that these FMO3 gene mutations were one of the causal factors for decreased FMO3 function resulting in trimethylaminuria. Inter-individual variations of FMO3-mediated microsomal oxygenation activities, levels of FMO3 protein and FMO3 mRNA, and its modification in liver microsomes from Japanese samples were observed. Both genetic polymorphisms in the 5′-upstream of the FMO3 gene and some hormonal changes related to menstruation may be causal factors for inter- and/or intra- individual expression levels of FMO3. To assess the palliative cares, it was found that absorbed levels of trimethylamine in vivo would be possibly controlled by selection of precursor foods like fish containing a variety of trimethylamine amounts. These lines of evidence suggest that individual differences of FMO3 are important determinants for the metabolic fate of dietary-derived trimethylamine.
1 0 0 0 OA ジクロフェナクの局所皮膚適用における副作用発現とリスク因子の評価
- 著者
- 大山 勝宏 清水 万紀子 山崎 浩史
- 出版者
- 一般社団法人日本医療薬学会
- 雑誌
- 医療薬学 (ISSN:1346342X)
- 巻号頁・発行日
- vol.40, no.5, pp.310-316, 2014-05-10 (Released:2015-05-10)
- 参考文献数
- 18
- 被引用文献数
- 1 1
A retrospective survey of a database containing patient backgrounds and prescribed drugs was conducted to elucidate the detailed characteristics and risk factors of adverse effects caused by topical dermatological formulations of diclofenac. A total of 145,478 patients who had been dispensed topical dermatological formulations of diclofenac at 466 community pharmacies belonging to Nihon Chouzai were included in the study. Of these, 580 patients had adverse effects. The incidence of adverse effects was significantly higher in the elderly (more than 65 years old) and in female patients. A variety of systemic adverse effects were evident in 19 patients. Approximately half of these adverse effects were related to the respiratory system, eg, asthma, but the other adverse effects (eg, edema, decreases in urinary volume, tremor and others) were not described in the drug package inserts. Data from patients with systemic adverse effects, and an age- and gender-matched control group of patients underwent multivariate logistic regression analysis. Asthma (odds ratio: 13.3, 95% confidence interval: 2.40 - 95.5, P = 0.004) and the number of co-administered drugs (odds ratio: 1.25, 95% confidence interval: 1.02 - 1.55, P = 0.035) were identified as risk factors for systemic adverse effects of topical dermatological formulations of diclofenac. Moreover, many of the co-administered drugs affected P450 enzymes other than P450 2C9, the main metabolizer of diclofenac. Therefore, to manage the risk of adverse events, it was concluded that various characteristics of concomitant medications and patient's medical history should be evaluated properly before topical dermatological formulations of diclofenac are prescribed.