Effects of ursodeoxycholic acid on the pharmacokinetics and pharmacodynamics of intravenous and oral midazolam in healthy volunteers
Effects of ursodeoxycholic acid on the pharmacokinetics and pharmacodynamics of intravenous and oral midazolam in healthy volunteers
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熊去氧胆酸对健康志愿者静脉注射和口服咪达唑仑药代动力学和药效学的影响
DOI：
10.1007/s00210-007-0217-z
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Hiroshi Watanabe
中科院分区：
文献类型：
--
作者：
D. Yan;Ying;S. Uchida;S. Misaka;Jinghui Luo;K. Takeuchi;N. Inui;S. Yamada;K. Ohashi;Hiroshi Watanabe
动物和体外研究表明，熊去氧胆酸（UDCA）可诱导细胞色素P450 3A（CYP 3A）表达并增强其活性。另一方面，Becquemont et al.证明UDCA对肠道CYP 3A活性无影响。本研究的目的是通过给予咪达唑仑（MDZ）（作为CYP 3A活性的特异性探针），研究UDCA对人体肠道和肝脏CYP 3A活性的影响。这是一项在14名健康志愿者中进行的随机、开放标签、交叉研究，分为两个阶段。志愿者口服UDCA（300 mg/天）或安慰剂9天。分别在第8天和第9天评估静脉注射MDZ（5 μg/kg）和口服MDZ（15 μg/kg）的药代动力学和药效学。通过测量峰值扫视速度、姿势距离、临界融合闪烁频率和视觉模拟量表来评估MDZ的药效学。UDCA不影响静脉和口服MDZ给药的药代动力学和药效学参数。我们的研究表明，UDCA的临床剂量不会影响肝脏和肠道CYP 3A活性，UDCA与CYP 3A底物之间的药物相互作用在人体中不太可能发生。
Animal and in vitro studies suggest that ursodeoxycholic acid (UDCA) can induce cytochrome P450 3A (CYP3A) expression and enhance its activities. On the other hand, Becquemont et al. demonstrated that UDCA had no influence on intestinal CYP3A activities. The aim of this study was to investigate the effects of UDCA on the intestinal and hepatic CYP3A activities by administration of midazolam (MDZ), as a specific probe for CYP3A activity, in humans. This was a randomized, open-label, crossover study with two phases in 14 healthy volunteers. The volunteers received UDCA (300 mg/day) or placebo orally for 9 days. The pharmacokinetics and pharmacodynamics of intravenous MDZ (5 μg/kg) and oral MDZ (15 μg/kg) were assessed on days 8 and 9, respectively. The pharmacodynamics of MDZ was estimated by measuring peak saccadic velocity, postural away length, critical fusion flicker frequency, and visual analogue scale. UDCA did not affect the pharmacokinetic and pharmacodynamic parameters of intravenous and oral MDZ administrations. Our study suggests that the clinical dosage of UDCA could not affect both hepatic and intestinal CYP3A activities and that the drug interaction between UDCA and substrates for CYP3A is unlikely in humans.
DOI：
10.1097/00008571-200310000-00003
发表时间：
2003-10-01
期刊：
PHARMACOGENETICS
影响因子：
--
作者：
Floyd, MD;Gervasini, G;Wilkinson, GR
通讯作者：
Wilkinson, GR
影响因子：
3.6
作者：
Domanski, TL;Finta, C;Zaphiropoulos, PG
通讯作者：
Zaphiropoulos, PG
影响因子：
4.7
作者：
T. Shimada;E. Gillam;P. Sandhu;Zuyu Guo;R. Tukey;F. Guengerich
通讯作者：
T. Shimada;E. Gillam;P. Sandhu;Zuyu Guo;R. Tukey;F. Guengerich