期刊
JOURNAL OF CLINICAL PHARMACOLOGY
卷 52, 期 10, 页码 1566-1573出版社
WILEY
DOI: 10.1177/0091270011419850
关键词
Midazolam; digoxin; telaprevir; drug interaction
资金
- Vertex Pharmaceuticals Incorporated (Vertex)
- Tibotec BVBA (Tibotec)
In this open-label study, 24 healthy volunteers received a single intravenous (IV) dose of 0.5 mg of midazolam on day 1 and a single oral dose each of 2 mg of midazolam and 0.5 mg of digoxin on day 3. Telaprevir 750 mg every 8 hours was administered from day 8 through day 23, along with a single IV dose of 0.5 mg of midazolam on day 17 and single oral doses of 2 mg of midazolam and 0.5 mg of digoxin on day 19. Midazolam, 1'-hydroxymidazolam, digoxin, and telaprevir concentrations in plasma and digoxin concentrations in urine were measured and pharmacokinetic parameters calculated. On comparing administration with versus without telaprevir, the geometric least squares mean ratios (with 90% confidence limits) for IV midazolam were 1.02 (0.80, 1.31) for maximum observed concentrations (C-max) and 3.40 (3.04, 3.79) for area under the curve from 0 to 24 hours (AUC(0-24h)); for oral midazolam 2.86 (2.52, 3.25) for C-max and 8.96 (7.75, 10.35) for AUC(0-24h); and for oral digoxin 1.50 (1.36, 1.65) for C-max and 1.85 (1.70, 2.00) for area under the curve from 0 to infinity (AUC(0-infinity)). Coadministration of telaprevir with oral midazolam resulted in approximately 3-fold decrease in the mean AUC(0-infinity) of 1'-hydroxymidazolam. The renal clearance of digoxin was similar with or without telaprevir. Results show that telaprevir is an inhibitor of CYP3A and P-glycoprotein.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据