Author(s)

Mei-Ling Yee, Hui-Hui Tan, Wan-Jin Sia, Wai-Ping Yau

Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore city, Singapore.
Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore city, Singapore.
Department of Pharmacy, Singapore General Hospital, Singapore city, Singapore.

Background: Tacrolimus pharmacokinetics has large inter-individual variability. Objectives: This study aimed to investigate 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 CYP3Aand 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 ratio 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 versus7.9 L/h, P = 0.033). Conclusions: Donor liver CYP3Apolymorphism could potentially affect tacrolimus C0/D ratio as early as the first week post liver transplant. Genotyping of liver donors may be useful to achieve the optimal drug concentration during this critical period.

Tacrolimus; Gene Polymorphisms; Liver Transplant; Pharmacokinetics

Yee, M. , Tan, H. , Sia, W. and Yau, W. (2013) Influences of Donor and Recipient Gene Polymorphisms on Tacrolimus Dosing and Pharmacokinetics in Asian Liver Transplant Patients. Open Journal of Organ Transplant Surgery, 3, 53-61. doi: 10.4236/ojots.2013.33011.