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- Title
Repaglinide-irbesartan drug interaction: effects of SLCO1B1 polymorphism on repaglinide pharmacokinetics and pharmacodynamics in Chinese population.
- Authors
Pei, Qi; Liu, Jun-Yan; Yin, Ji-Ye; Yang, Guo-Ping; Liu, Shi-Kun; Zheng, Yi; Xie, Pan; Guo, Cheng-Xian; Luo, Mi; Zhou, Hong-Hao; Li, Xi; Liu, Zhao-Qian
- Abstract
Purpose: 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.Methods: 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.Results: 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 minimum blood glucose concentration [Cmin] decreased 33.8% (P = 0.005). No significant change was observed in repaglinide exposure in subjects with SLCO1B1 c.521 TC genotype in presence or absence of irbesartan.Conclusion: SLCO1B1 c.521 T>C polymorphism affects the PK of repaglinide in Chinese population. Irbesartan increased repaglinide exposure in subjects with SLCO1B1 c.521 TT genotype, but not SLCO1B1 c.521 TC genotype.
- Subjects
CHINA; BLOOD sugar monitoring; CELL lines; DRUG interactions; GENETIC polymorphisms; HYPOGLYCEMIC agents; PEPTIDES; IRBESARTAN; LOSARTAN; VALSARTAN; IN vitro studies; MEMBRANE transport proteins; PHARMACODYNAMICS
- Publication
European Journal of Clinical Pharmacology, 2018, Vol 74, Issue 8, p1021
- ISSN
0031-6970
- Publication type
Article
- DOI
10.1007/s00228-018-2477-6