Influence of CYP3A5 genetic polymorphism on cyclosporine A metabolism and elimination in Chinese renal transplant recipients.Author information 1Department of Clinical Pharmacology, General Hospital of Nanjing Military Area, Nanjing 210002, China.
Abstract 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.
Acta Pharmacol Sin. 2006 Nov;27（11）:1504-8. PMID: 17049128 [PubMed - indexed for MEDLINE]
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