Influence of CYP3A5 genetic polymorphism on cyclosporine A metabolism and elimination in Chinese renal transplant recipients

Aim： To investigate whether the CYP3A5＊3 polymorphism would affect cyclosporine A （CsA） metabolism in Chinese renal transplant patients. Methods： The CYP3A5＊3 genotype was determined in Chinese renal transplant recipients using polymerase chain reaction and amplification of specific alleles （PCR-ASA）. The concentrations of CsA and metabolites were separately measured by fluorescence polarization immunoassay and dose-adjusted trough concentrations and metabolic ratio （MR） values were calculated. Results： The trough concentrations adjusted with the dose was significantly higher in the wild allele carriers compared to both the homozygous （＊3＊3） and heterozygous variants （＊1＊3）. However, no significant difference was found for the dose-adjusted metabolite concentrations. The MR values for the 3 genotype groups were as follows： 0.92±0.62 for CYP3A5＊3/ ＊3 （n=14）, 0.99±0.51 for CYP3A5＊1/＊3 （n=15）, and 1.45±0.62 for CYP3A5＊1/＊1 （n=9）, respectively. Post hoc comparisons showed that only the MR values between the CYP3A5＊3/＊3 group and the CYP3A5＊1/＊1 group were significantly different. Conclusion： The CYP3A5＊3 polymorphism exerted little effect on cyclosporine metabolism. The MR may be a more accurate indicator for therapeutic drug monitoring, considering its integrated information on body exposure of both parent drugs and metabolites.