Title Effects of CYP2C8 and SLCO1B1 Genetic Polymorphisms on Repaglinide Pharmacokinetics: A Systematic Review and Meta-Analysis
Authors Zhou, Shuang
Xiang, Qi
Mu, Guangyan
Ma, Lingyue
Chen, Shuqing
Xie, Qiufen
Zhang, Zhuo
Cui, Yimin
Affiliation Peking Univ, Hosp 1, Dept Pharm, Beijing 100034, Peoples R China
Keywords Repaglinide
T2DM
CYP2C8
SLCO1B1
metabolism
pharmacokinetics
Issue Date 2019
Publisher CURRENT DRUG METABOLISM
Abstract Objective: The purpose of this systematic review and meta-analysis was to summarize the potential impact of CYP2C8 and SLCO1B1 genetic polymorphisms on repaglinide pharmacokinetics. Methods: A systematic search was conducted using electronic databases. Eligible studies reported data from pharma-cokinetic evaluations of repaglinide in healthy adults according to different categories of CYP2C8 and SLCO1B1 genetic polymorphisms. Results: Six studies including a total of 191 participants met the inclusion criteria. We noted that CYP2C8 *1/*3 carriers exhibited lower AUC((0-infinity)) (SMD: -0.77; 95% CI: -1.23 to -0.30; P=0.001) and C-max (SMD: -0.94; 95% CI: 1.41 to -0.47; P<0.001) than CYP2C8 *1/*1 carriers. There were no significant differences in AUC((0-infinity)), C-max, t(1/2) and mean change in blood glucose concentration between *1/*4 and *1/*1 carriers. Further, *3/*3 carriers had lower Cmax (SMD: -1.42; 95% CI: -2.66 to -0.17; P=0.026) than *1/*1 carriers. Additionally, *3/*3 carriers had lower Cmax than *1/*3 carriers (SMD: -1.20; 95% CI: -2.40 to -0.00; P=0.050). Finally, we noted that repaglinide pharmacokinetics did not differ by SLCO1B1 genotype. Conclusion: The current systematic review and meta-analysis indicated that the genotype of CYP2C8, but not SLCO1B1, may affect repaglinide pharmacokinetics. However, because of the comparatively insufficient number of published studies included, our conclusions require support from additional studies.
URI http://hdl.handle.net/20.500.11897/551821
ISSN 1389-2002
DOI 10.2174/1389200220666190111114146
Indexed SCI(E)
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