Impact of CYP3A4/5 and ABCB1 polymorphisms on tacrolimus exposure and response in pediatric primary nephrotic syndrome.

Abstract

Aim: To evaluate the impact of CYP3A4*1G, CYP3A5*3 and ABCB1-C3435T polymorphisms on tacrolimus concentrations, efficacy and tolerance in pediatric primary nephrotic syndrome. Methods: Dose-adjusted concentrations (C0/D), daily dose, frequency and time to relapse, cumulative remission days, and adverse reactions in 65 Chinese patients with various genotypes were retrospectively collected and compared. Results: C0/D increased in CYP3A4*1/*1, CYP3A5*3/*3 and CYP3A4*1/*1-3A5*3/*3 diplotype carriers by 38.4, 69.7 and 40.9% compared with CYP3A4*1/*1G, CYP3A5*1/*3 and noncarriers, respectively. Recurrence risks were decreased in CYP3A4*1/*1 (0.43 of hazard ratio to *1/*1G) and CYP3A5*3/*3 carriers (0.43 of hazard ratio to *1/*3). None of polymorphisms was linked to adverse reactions. Conclusion: The genotypes of CYP3A4*1G and CYP3A5*3 rather than ABCB1-C3435T potentially predicted tacrolimus exposure and clinical response in pediatric primary nephrotic syndrome.