Influences of Donor and Recipient Gene Polymorphisms on Tacrolimus Dosing and Pharmacokinetics in Asian Liver Transplant Patients

Copyright © 2013 Mei-Ling Yee et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: Tacrolimus pharmacokinetics has large inter-individual variability. Objectives: This study aimed to in-vestigate the impact of donor and recipient gene polymorphisms on tacrolimus dosing and pharmacokinetics in Asian liver transplant patients. Methods: Steady-statetacrolimus concentrations at 0, 1, 2, 4 and 6 h were measured. Pharma-cokinetic parameters were estimated with a one-compartment linear model using WinNonlin 6.1 program. DNA from donor liver and recipient blood samples were genotyped for CYP3A and ABCB1 polymorphisms. Results: A total of 13 donors and 17 recipients were included. Donor genotypes influenced tacrolimus trough concentration-to-dose (C0/D) ratio only at Week 1. Patients with liver grafts from CYP3A5 expressors (*1*1 and *1*3) achieved lower mean C0/D ra-tio than those with grafts from non-expressors (*3*3) (64.48 versus 129.21 (mcg/L)/(mg/kg/day), P = 0.040). Hence, the dose required to achieve target concentration in patients with donor genotype CYP3A5 expressors was higher than non-expressors (0.12 versus 0.08 mg/kg, P = 0.045). Recipient with ABCB1-C3435T genotype TT demonstrated higher apparent oral clearance of tacrolimus as compared to genotype CC (17.7 versus 7.9 L/h, P = 0.033). Conclusions: Do-nor liver CYP3A polymorphism could potentially affect tacrolimus C0/D ratio as early as the first week post live