Effect Of Cyp3a5 Polymorphism On The Pharmacokinetics Of Tacrolimus And Acute Rejection In Renal Transplant Recipients: Experience At A Single Centre

AimAs a substrate of cytochrome P450 (CYP) 3A5, tacrolimus is characterised by a narrow therapeutic index and large inter-individual variability. Our objective was to determine the influence of CYP3A5 genetic polymorphisms on tacrolimus pharmacokinetics and acute rejection in Chinese renal transplant recipients.MethodsThirty-five renal recipients treated with tacrolimus in our centre were genotyped for CYP3A5 single nucleotide polymorphisms, CYP3A5*1 (6986A) and CYP3A5*3 (6986G). These patients were divided into the following three groups: CYP3A5*1*1 homozygous carriers, CYP3A5*3*3 homozygous carriers and CYP3A5*1*3 heterozygous carriers. Doses administered at 1week and at 1, 6 and 12months posttransplantation were recorded. Whole blood concentration was measured using the enzyme-multiplied immunoassay technique. Biopsy-proven acute rejection episodes (BPAR) reported during the first year after transplant were obtained retrospectively.ResultsThe concentration/dose ratios of CYP3A5*3 homozygous carriers at 1week and at 1, 6 and 12months were significantly higher than the ratios among CYP3A5*1 carriers (CYP3A5*1*1 and CYP3A5*1*3, p<0.05). BPAR occurred in four patients during the first month after transplant, three of whom were CYP3A5*1 carriers.ConclusionCYP3A5 genetic polymorphism is associated with the concentration/dose ratio of tacrolimus in Chinese renal recipients. Patients with CYP3A5*1*1 genotypes require higher doses of tacrolimus to achieve the target concentration and may be at risk of acute rejection soon after transplant because of inadequate immunosuppression. Screening for this polymorphism could be helpful in choosing the suitable calcineurin inhibitors and determining the suitable initial dose.