P033 : IMPACT OF CYP3A5 POLYMORPHISMS ON THE METABOLISM OF TACROLIMUS IN RENAL TRANSPLANT RECIPIENTS DURING A 4-YEAR FOLLOW-UP

Abstract

Aim To analyze the association between CYP3A5 single nucleotide polymorphisms (SNPs) and tacrolimus (Tac) or cyclosporine (CsA) level in renal transplant recipients during a 4-year follow-up. Methods 103 renal transplant patients were recruited and assigned into three groups according to their CYP3A5 allele ∗ 3/ ∗ 3, ∗ 1/ ∗ 3, or ∗ 1/ ∗ 1. The concentrations of Tac or CsA at time zero (C0) were measured before the drug administration. And the association between different alleles with Tac or CsA dose-adjusted C0 were further analyzed. Results During the first month after transplantation, recipients with CYP3A5 ∗ 3/ ∗ 3 allele exhibited significantly higher Tac C0 than the recipients with CYP3A5 ∗ 1/ ∗ 1 allele. The Tac dose/day used for recipients with CYP3A5 ∗ 3/ ∗ 3 allele was significantly lower than that for recipients with CYP3A5 ∗ 1/ ∗ 1 or CYP3A5 ∗ 1/ ∗ 3 allele. The Tac C0 of recipients with CYP3A5 ∗ 3/ ∗ 3 allele was significantly difference than that of the recipients with CYP3A5 ∗ 1/ ∗ 3 and CYP3A5 ∗ 1/ ∗ 1 allele at 3 months, 6 months, 12 months, 24 months and 48 months respectively during the 4-year follow-up after transplantation. The trough concentrations/doses of CsA were not associated with the CYP3A5 SNPs. Conclusion Patients with homozygous CYP3A5 ∗ 3/ ∗ 3 allele need less dosage of Tac to maintain a therapeutic concentration after renal transplantation.