Effects of CYP2C8 and SLCO1B1 Genetic Polymorphisms on Repaglinide Pharmacokinetics: A Systematic Review and Meta-Analysis

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Author(s): Shuang Zhou, Qian Xiang, Guangyan Mu, Lingyue Ma, Shuqing Chen, Qiufen Xie, Zhuo Zhang, Yimin Cui*.

Journal Name: Current Drug Metabolism

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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.

Method: A systematic search was conducted using electronic databases. Eligible studies reported data from pharmacokinetic 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-∞) (SMD: -0.77; 95%CI: -1.23 to -0.30; P=0.001) and Cmax (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-∞), Cmax, t1/2 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.

Keywords: Repaglinide, T2DM, CYP2C8, SLCO1B1, metabolism, pharmacokinetics.

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(E-pub Ahead of Print)
DOI: 10.2174/1389200220666190111114146