Kyrklund Carl, Backman Janne T, Neuvonen Mikko, Neuvonen Pertti J
Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
Br J Clin Pharmacol. 2004 Feb;57(2):181-7. doi: 10.1046/j.1365-2125.2003.01972.x.
Previous work has shown that rifampicin, a potent inducer of several cytochrome P450 (CYP) enzymes and transporters, decreased the plasma concentrations of simvastatin acid by more than 90%. This study was conducted to investigate the effect of rifampicin on the pharmacokinetics of pravastatin.
In a randomised, cross-over two-phase study with a washout of 4 weeks, 10 healthy volunteers received a 5-day pretreatment with rifampicin (600 mg daily) or placebo. On day 6, a single 40 mg dose of pravastatin was administered orally. Plasma concentrations of pravastatin were measured up to 12 h by a sensitive LC-MS-MS method.
During the rifampicin phase, the mean total area under the plasma concentration-time curve of pravastatin [AUC(0-infinity )] was 69% (range 24-220%) of the corresponding value during the placebo phase (P < 0.05, 95% confidence interval for the difference -51.9 - -0.4 ng ml-1.h). In five of the 10 subjects the AUC(0-infinity ) of pravastatin during the rifampicin phase was 50% or less of that during the placebo phase. Rifampicin had no significant effect on the peak concentration, elimination half-life or renal clearance of pravastatin.
Rifampicin caused a statistically significant decrease in the plasma concentration of pravastatin given as a single oral dose to healthy subjects. However, the effect of rifampicin varied greatly between subjects. The mean rifampicin-induced decrease in pravastatin concentration was considerably smaller than that observed previously for simvastatin.
先前的研究表明，利福平作为几种细胞色素P450（CYP）酶和转运蛋白的强效诱导剂，可使辛伐他汀酸的血浆浓度降低90%以上。本研究旨在探讨利福平对普伐他汀药代动力学的影响。
在一项为期4周洗脱期的随机、交叉两阶段研究中，10名健康志愿者接受了利福平（每日600mg）或安慰剂的5天预处理。在第6天，口服单剂量40mg普伐他汀。采用灵敏的液相色谱-串联质谱法测定普伐他汀血浆浓度长达12小时。
在利福平阶段，普伐他汀血浆浓度-时间曲线下的平均总面积[AUC(0-∞)]为安慰剂阶段相应值的69%（范围24%-220%）（P<0.05，差异的95%置信区间为-51.9至-0.4ng/ml·h）。10名受试者中有5名在利福平阶段普伐他汀的AUC(0-∞)为安慰剂阶段的50%或更低。利福平对普伐他汀的峰浓度、消除半衰期或肾清除率无显著影响。
利福平使健康受试者单次口服普伐他汀后的血浆浓度在统计学上显著降低。然而，利福平的影响在受试者之间差异很大。利福平引起的普伐他汀浓度平均降低幅度远小于先前观察到的辛伐他汀。
