%0 Journal Article
%T Influences of Donor and Recipient Gene Polymorphisms on Tacrolimus Dosing and Pharmacokinetics in Asian Liver Transplant Patients
%A Mei-Ling Yee
%A Hui-Hui Tan
%A Wan-Jin Sia
%A Wai-Ping Yau
%J Open Journal of Organ Transplant Surgery
%P 53-61
%@ 2163-9493
%D 2013
%I Scientific Research Publishing
%R 10.4236/ojots.2013.33011
%X <b><span>Background</span></b><b><span>: </span></b><span>Tacrolimus pharmacokinetics has large inter-individual variability. <b>Objectives</b></span><b><span>:</span></b><span> This study aimed to in</span><span>vestigate the impact of donor and recipient gene polymorphisms on tacrolimus dosing and pharmacokinetics in Asian liver transplant patients.</span><span> </span><b><span>Methods</span></b><b><span>:</span><span> </span></b><span>Steady-statetacrolimus concentrations at 0, 1, 2, 4 and 6 h were measured. Pharma</span><span>- </span><span>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. <b>Results</b></span><b><span>:</span><span> </span></b><span>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 (</span><sup><span>*</span></sup><span>1</span><sup><span>*</span></sup><span>1 and </span><sup><span>*</span></sup><span>1</span><sup><span>*</span></sup><span>3) achieved lower mean C0/D ra</span><span>tio than those with grafts from non-expressors (</span><sup><span>*</span></sup><span>3</span><sup><span>*</span></sup><span>3) (64.48 versus 129.21</span><span> </span><span>(mcg/L)/(mg/kg/day), P</span><span> </span><span>=</span><span> </span><span>0.040). Hence, the dose required to achieve target concentration in patients with donor genotype CYP3A5 expressors was higher than non-expressors (</span><span>0.12 versus 0.08 mg/kg, P</span><span> </span><span>=</span><span> </span><span>0.045)</span><span>. 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</span><span> </span><span>=</span><span> </span><span>0.033).</span><span> </span><b><span>Conclusions</span></b><b><span>:</span><span> </span></b><span>Do</span><span>nor liver</span><span> </span><span>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 pe</span><span>riod.</span>
%K Tacrolimus
%K Gene Polymorphisms
%K Liver Transplant
%K Pharmacokinetics
%U http://www.scirp.org/journal/PaperInformation.aspx?PaperID=35992