期刊
XENOBIOTICA
卷 37, 期 4, 页码 416-426出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/00498250601188808
关键词
pravastatin; gemfibrozil; OAT; drug-drug interaction
Coadministration of gemfibrozil (600 mg, b. i. d., 3 days) with pravastatin (40 mg/day) decreased the renal clearance of pravastatin by approximately 40% in healthy volunteers. To investigate the mechanism of this drug-drug interaction in the renal excretion process, we undertook an uptake study of pravastatin using human organic anion transporters (hOATs)-expressing S2 cells. hOAT3 and hOAT4 transported pravastatin in a saturatable manner with Michaelis-Menten constants of 27.7 mu M and 257 mu M respectively. On the other hand, hOAT1 and hOAT2 did not transport pravastatin. Gemfibrozil and its glucuronide and carboxylic metabolite forms inhibited the uptake of pravastatin by hOAT3 with IC50 values of 6.8 mu M, 19.7 mu M and 5.4 mu M, respectively. Considering the plasma concentrations of gemfibrozil and its metabolites in humans, the inhibition of hOAT3-mediated pravastatin transport by gemfibrozil and its metabolites would lead to a decrease in the renal clearance of pravastatin in clinical settings.
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