The effect of SLCO1B1*15 on the disposition of pravastatin and pitavastatin is substrate dependent:: the contribution of transporting activity changes by SLCO1B1*15
The effect of SLCO1B1*15 on the disposition of pravastatin and pitavastatin is substrate dependent:: the contribution of transporting activity changes by SLCO1B1*15
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DOI：
10.1097/fpc.0b013e3282fb02a3
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发表时间：
2008-05-01
影响因子：
2.6
通讯作者：
Shin, Jae-Gook
中科院分区：
文献类型：
--
作者：
Deng, Jian Wei;Song, Im-Sook;Shin, Jae-Gook
Objective This study was addressed to understand the underlying mechanism of the substrate-dependent effect of genetic variation in SLCO1B1, which encodes OATP1B1 (organic anion transporting polypeptide) transporter, on the disposition of two OATP1B1 substrates, pravastatin and pitavastatin, in relation to their transport activities.Methods The uptake of pravastatin, pitavastatin, and fluvastatin was measured in oocytes overexpressing SLCO1B1*1a and SLCO1B1*15 to compare the alterations of in-vitro transporting activity. After 40-mg pravastatin or 4-mg pitavastatin was administered to 11 healthy volunteers with homozygous genotypes of SLCO1B1*1a/*1a and SLCO1B1*15/*15, the pharmacokinetic parameters of pravastatin and pitavastatin were compared among participants with SLCO1B1*1a/*1a and SLCO1B1*15/*15 genotypes.Results The uptake of pravastatin and pitavastatin in SLCO1B1*15 overexpressing oocytes was decreased compared with that in SLCO1B1*15, but no change occurred with fluvastatin. The fold change of in-vitro intrinsic clearance (CIint) for pitavastatin in SLCO1B1*15 compared with SLCO1B1*1a was larger than that of pravastatin (P
