Abstract:

BACKGROUND: The calcineurin inhibitor tacrolimus is widely used to prevent allograft rejection after liver transplantation. It has a narrow therapeutic index and shows considerable interindividual differences in its pharmacokinetics.
OBJECTIVE: To evaluate retrospectively the effect of genetic polymorphisms of ABCB1 on tacrolimus dosage and dosage adjusted trough blood concentration during the early period after liver transplantation in patients.
METHODS: Sixty-seven liver transplantation recipients were genotyped by DNA sequencing for ABCB1. Tacrolimus whole blood levels were measured by enzyme-linked immunospecific assay. Dose-adjusted trough blood concentrations (C) were determined and compared among different genotype groups.
RESULTS AND CONCLUSION: The tacrolimus dosage had great variation between individuals. A synonymous single nucleotide polymorphism (SNP) of ABCB1 in various exons was different. Furthermore, ABCB1 3435C>T polymorphisms was significantly correlated with tacrolimus dose-adjusted pre-dose concentrations at various time points. The present study shows that genetic polymorphisms in ABCB1 may be responsible, in part, for the large interindividual variability of tacrolimus pharmacokinetics during the early period after liver transplantation in patients. Patients in ABCB1 3435C>T wild-type expressors require a high dose of tacrolimus to reach target levels compared with mutator expressors. Genotyping future transplant recipients for ABCB1 polymorphisms, therefore, could have the potential to individualize better tacrolimus immunosuppressive therapy and enhance drug safety.