Influence of C Upsilon P2C9 Genetic Polymorphisms on the Pharmacokinetics of Losartan and Its Active Metabolite E-3174: A Systematic Review and Meta-Analysis

Abstract

This study aimed to investigate the influence of C Upsilon P2C9 genetic polymorphisms on the pharmacokinetics of losartan and its active metabolite, E-3174, through a systematic review and meta-analysis. Eight studies published before March 2021 were included in this study. We used PubMed, the Cochrane Library, EMBASE, and Web of Science, based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The data analysis was conducted through Review Manager (RevMan), version 5.3, and R software. We found that healthy volunteers with C Upsilon P2C9*2 or *3 carriers had higher area under the curve (AUC(0-infinity)) of losartan (mean difference (MD) 0.17 mu g.h/mL; 95% confidence intervals (CI): 0.04, 0.29) and lower AUC(0-infinity) of E-3174 (MD -0.35 mu g.h/mL; 95% CI: -0.62, -0.08) than those with C Upsilon P2C9*1/*1. Subjects with C Upsilon P2C9*2 or *3 carriers showed lower maximum concentration (C-max) of E-3174 than those with C Upsilon P2C9*1/*1 (MD -0.13 mu g/mL; 95% CI: -0.17, -0.09). For half-life, subjects with C Upsilon P2C9*2 or *3 carriers had longer half-lives of losartan and E-3174 than those with C Upsilon P2C9*1/*1 (MD 0.47 h; 95% CI: 0.32, 0.61 and MD 0.68 h; 95% CI: 0.44, 0.92, respectively). This meta-analysis suggests that the pharmacokinetics of losartan and E-3174 are associated with the C Upsilon P2C9 polymorphisms