The Influence of CYP3A5 and MDR1(ABCB1) polymorphisms on the pharmacokinetics of tacrolimus in renal transplant recipients

Objective To investigate the influence of CYP3A5 and MDRl genetic polymorphisms on tacrolimus pharmacokinetics in renal transplant recipients for the rational administration in clinical practice.Methods The blood concentration was measured and pharmacokinetic parameters of tacrolimus were calculated in steady-state on day 28 after transplantation.Polymerase chain reaction and restriction fragment length polymorphisms were used for CYP3A5 and MDRl polymorphisms,respectively.Results The dose-adjusted area under the concentration-time curve(AUC0-12) was significantly lower among CYP3A5*1 carriers than those bearing CYP3A5 * 3/ * 3.In the following study,a distinction was made between carriers of CYP3A5 * 1/ * 1 + CYP3A5 * 1/ * 3 and CYP3A5 * 3/ * 3 to investigate the influence of the MDR1C3435T mutation on tacrolimus pharmacokinetics. The MDRl C3435T polymorphisms did not affect any tacrolimus pharmacokinetic parameter in either group.Conclusion Renal transplant recipients who were CYP3A5 * 1 carriers required a higher dose of tacrolimus than those with CYP3A5 * 3/ * 3.In contrast, MDRl C3435T polymorphism was not an important factor in tacrolimus pharmacokinetics.Pharmacogenetic methods could be employed to help the dose selection and to individualize immunosuppressive therapy prospectively.