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Effect of SLCO1B1 genetic polymorphism on the pharmacokinetics of nateglinide
Author(s) -
Zhang Wei,
He YiJing,
Han ChunTing,
Liu ZhaoQian,
Li Qing,
Fan Lan,
Tan ZhiRong,
Zhang WeiXia,
Yu BangNing,
Wang Dan,
Hu DongLi,
Zhou HongHao
Publication year - 2006
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2006.02686.x
Subject(s) - nateglinide , slco1b1 , pharmacokinetics , single nucleotide polymorphism , pharmacology , medicine , genotype , chemistry , endocrinology , gene , biochemistry , type 2 diabetes , diabetes mellitus
Aims Nateglinide is a meglitinide analogue with antidiabetic action. A recent study showed that SLCO1B1 (which codes the OATP1B1 gene, also known as OATP‐C, OATP2 ) is a major determinant which markedly affects the pharmacokinetics of repaglinide. Our objective was to assess the association between single nucleotide polymorphisms (SNPs) of SLCO1B1 and the pharmacokinetics of nateglinide. Methods Seventeen healthy volunteers with different SLCO1B1 genotypes (11 with 521TT, four with 521TC and two with 521CC) were enrolled in this study. Each was given a single oral dose of 90 mg nateglinide. Plasma concentrations of nateglinide were measured up to 8 h by HPLC. Results The C max and AUC(0,∞) of nateglinide were 83% ( P = 0.002) and 82% ( P = 0.001) higher in the SLCO1B 1521TC subjects ( n = 4), and 76% ( P = 0.016) and 108% ( P = 0.001) higher in the SLCO1B 1521CC subjects ( n = 2) than in the SLCO1B 1521TT subjects ( n = 11), respectively. The t 1/2 of nateglinide in SLCO1B 1521CC subjects was 78% longer than that in 521TT subjects ( P = 0.036). The difference in t max values among the three genotypic groups was not statistically significant. Conclusions Our results suggest that OATP1B1‐mediated hepatic uptake of nateglinide may be the prior step for its metabolism and elimination. SLCO1B 1521T > C SNP might play an important role in the pharmacokinetics of nateglinide.