Genetic polymorphisms of CYP3A5 genes and concentration of the cyclosporine and tacrolimus

Abstract Objective CYP3A is the major enzyme responsible for metabolism of the calcineurin inhibitors cyclosporine (CsA) and tacrolimus. Our objective was to determine the relationship between genetic polymorphisms of CYP3A5 with respect to interindividual variability in CsA and tacrolimus pharmacokinetics. Methods Kidney transplant recipients receiving CsA (n = 137) or tacrolimus (n = 30) were genotyped for CYP3A5*3 and *6 by a PCR/RFLP method. The patients were grouped according to the CYP3A5 genotype. Dose-adjusted trough levels were correlated with the corresponding genotype. Results At 3, 6, and 12 months, the tacrolimus dose-adjusted trough levels (dose-adjusted C0) showed a statistically significant difference between the group of CYP3A5*3/*3 (n = 19) and the group of CYP3A5*1 allele carriers. The former was higher than the latter. The CsA dose–adjusted C0 and the actual C0 did not display a significant relation ( P Conclusion Patients with the CYP3A5*3/*3 genotype require less tacrolimus to reach target concentrations compared to those with the CYP3A5*1 allele.