Effect of pitavastatin in different SLCO1B1 backgrounds on repaglinide pharmacokinetics and pharmacodynamics in healthy Chinese males.
PAKISTAN JOURNAL OF PHARMACEUTICAL SCIENCES(2013)
Abstract
The effect of pitavastatin and SLCO1B1 genetic background on the pharmacokinetic and pharmacodynamic properties of repaglinide was investigated. In this randomized, placebo-controlled, crossover study, twelve healthy Chinese males were administered with pitavastatin 4 mg/d or the placebo for 5 d followed by repaglinide 4 mg given orally on d 5. Plasma repaglinide and glucose levels were measured by liquid chromatography-tandem mass spectrometry (LC/MS/MS) and the glucose oxidase method, respectively. Treatment with pitavastatin significantly increased the peak plasma concentration (C-max) of repaglinide (P=0.003) in SLCO1B1*1b homozygotes (P=0.015) and SLCO1B1*15 carriers (P=0.031). Treatment with pitavastatin led to a marginal increase in the area under plasma concentration-time curve from 0 h to infinity (AUC(0 ->infinity)) of repaglinide (P=0.091). There was no significant difference in pharmacokinetic parameters or hypoglycemic effects of repaglinide among SLCO1B1 genotypes in either the pitavastatin or control group. Pitavastatin increased the Cmax of the plasma concentration of repaglinide in an SLCO1B1 genotype dependent manner, but had no apparent effect on the pharmacodynamics of repaglinide in healthy volunteers. The p values for this statement were not reported.
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Key words
Pitavastatin,repaglinide,SLCO1B1,pharmacokinetics,pharmacodynamics.
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