G-011 INFLUENCE OF PITAVASTARIN AND SLCO1B1 POLYMORPHISMS ON REPAGLINIDE PHARMACOKINETICS AND PHARMACODYNAMICS IN HEALTHY CHINESE MALE SUBJECTS

Abstract

Background This study investigated the effect of pitavastatin and SLCO1B1 genetic polymorphisms on the pharmacokinetics and pharmacodynamics of repaglinide. Methods In a randomized, placebo-controlled, crossover study, twelveSLCO1B1-genotyped healthy Chinese male volunteers were given daily doses of 4 mg pitavastatin or placebo for 5 days, followed by 4 mg oral dose of repaglinide on day 5. Plasma concentrations of repaglinide and blood glucose were measured by liquid chromatography-tandem mass spectrometry (LC/MS/MS) system and glucose oxidase method, respectively. Pharmacokinetic parameters were obtained by DAS Ver 2.0. Results Pitavastatin increased the peak plasma concentration (Cmax) of repaglinide significantly (P = 0.003), and the increase in Cmax was limited to participants with the SLCO1B1*1b/*1b genotype (P = 0.015) and carriers of the SLCO1B1*15 haplotype (P = 0.031). Pitavastatin can also increased the area under plasma concentration–time curve from 0 h to infinity (AUC0→∞) of repaglinide slightly (P = 0.091). No significant difference in the pharmacokinetic parameters and blood glucose-lowering effects of repaglinide were observed among SLCO1B1 genotype groups in either the placebo- or the pitavastatin-treatment phase. Conclusion Pitavastatin increased plasma concentrations of repaglinide in an SLCO1B1 genotype dependent manner, but had no effect on the pharmacodynamics of repaglinide in healthy volunteers.