Effects of SLCO1B1 polymorphisms on the pharmacokinetics and pharmacodynamics of repaglinide in healthy Chinese volunteers

European Journal of Clinical Pharmacology
Jiake HeXijing Chen

Abstract

Repaglinide is commonly used in the treatment of patients with type 2 diabetes mellitus to reduce postprandial hyperglycemia. The objective of this research was to study the effects of SLCO1B1 polymorphisms on the pharmacokinetics and pharmacodynamics of repaglinide in healthy Chinese volunteers. A total of 22 healthy young male participants were recruited from a pool of pharmacogenetically characterized participants genotyped for SLCO1B1, CYP3A4, and CYP2C8 SNPs by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Volunteers with CYP2C8*3 and CYP3A4*4 alleles were excluded from the clinical study. Then selected volunteers took part in the clinical pharmacokinetic study, receiving 2 mg repaglinide. Healthy participants with SLCO1B1*1A/*1B or *1A/*1A genotype and SLCO1B1 *15/*1A or *5/*1A genotype had significantly higher AUC(0-∞) than participants with SLCO1B1*1B/*1B genotype, with the former showing an increase over the latter of 39.81 and 42.09%, respectively (P = 0.028, 0.032). The clearance in the former two genotype groups was significantly attenuated (by 27.39 and 28.55%, respectively) compared with individuals with SLCO1B1*1B/*1B genotype (P = 0.015, 0.019). No significant differences in bloo...Continue Reading

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Jun 29, 2013·European Journal of Clinical Pharmacology·Qing-qing DuLing Wang
Sep 29, 2012·Molecular Diagnosis & Therapy·Gaia Chiara Mannino, Giorgio Sesti
May 31, 2013·Clinical Pharmacokinetics·N van LeeuwenL M 't Hart
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Sep 16, 2020·Diabetes Therapy : Research, Treatment and Education of Diabetes and Related Disorders·Zhiwei ZengTao Sun
Mar 15, 2012·Current Opinion in Pediatrics

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