Effect of Wuzhi preparations on tacrolimus in CYP3A5 expressers during the early period after transplantation: A real-life experience from heart transplant recipients

Abstract

BackgroundGenetic polymorphisms and drug interactions are associated with tacrolimus exposure. This study aimed to evaluate the effect of Wuzhi (WZ) preparations on tacrolimus (TAC) concentration and dose requirements in heart transplant recipients with the CYP3A5*1 allele during the early period after transplantation. MethodsA total of 167 adult heart transplant recipients with the CYP3A5*1 allele were included and divided into the WZ group (n = 115) and the WZ-free group (n = 52). Blood trough concentrations of TAC were detected and the dose-adjusted concentration (C0/D) and dose requirement for achieving the TAC therapeutic range were compared between the two groups. The change in C0/D and dose of TAC were evaluated before and after co-administration with WZ preparations. ResultsNo significant differences in TAC C0/D and dose requirement were observed between the WZ and WZ-free groups. However, the TAC C0/D in the WZ group was significantly increased an average of 2.10-fold after co-administration of WZ. Moreover, the degree of elevation was related to the dose of the active ingredient (Schisantherin A). Furthermore, ALT, AST, and TB levels were significantly reduced after administration of WZ preparations. ConclusionCo-administration of the WZ/TAC preparation, in heart transplant recipients carrying the CYP3A5*1 allele, considerably increased TAC concentration (C0/D) while decreased high levels of leading indicators in the liver function. More importantly, the effect of the WZ/TAC preparation on C0/D was a dose-dependent event. However, our finding needs to be further confirmed in a larger sample size.