Repaglinide-irbesartan drug interaction: effects of SLCO1B1 polymorphism on repaglinide pharmacokinetics and pharmacodynamics in Chinese population

European Journal of Clinical Pharmacology
Qi PeiZhao-Qian Liu

Abstract

On account of the potential inhibition of OATP1B1 (organic anion transporting polypeptide) by angiotensin II receptor blockers (ARBs) and the effects of SLCO1B1 (solute carrier organic anion transporter family member) polymorphism, the aim of current study is to assess the impact of ARBs on the pharmacokinetics (PK) and pharmacodynamics (PD) of repaglinide in Chinese healthy volunteers with different SLCO1B1 genotypes. The in vitro study was conducted on irbesartan, valsartan, olmesartan, and losartan by using HEK293 cells transfected with OATP1B1. Data on drug interactions between repaglinide and irbesartan from 21 healthy Chinese-Han male volunteers were collected and analyzed. IC50 from in vitro study suggested irbesartan was the most potent inhibitor of OATP1B1 transporter. Clinical data from single dose of repaglinide indicated SLCO1B1 c.521 T>C polymorphism influenced the PK and PD of repaglinide in healthy Chinese-Han male volunteers. In subjects with SLCO1B1 c.521 TT genotype, irbesartan comedication increased the exposure of repaglinide. In details, the peak plasma concentration [Cmax] increased 84% (P = 0.003) and the area under the curve of plasma concentration 0-8 h [AUC0-8] increased 34% (P = 0.004), while the mini...Continue Reading

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Citations

Jun 11, 2019·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Yingmin NieChunshan Gui
Sep 16, 2020·Diabetes Therapy : Research, Treatment and Education of Diabetes and Related Disorders·Zhiwei ZengTao Sun
Nov 2, 2021·Expert Opinion on Drug Metabolism & Toxicology·Veronica Di PaoloLuigi Quintieri

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Methods Mentioned

BETA
genotyping

Software Mentioned

Drug and Statistics Software ( DAS
SPSS

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