Effect of CYP3 A Polymorphism on Cyclosporine Individual Dosage and Blood Concentration in Renal Transplant Recipients / 中国药师

ABSTRACT

Objective:To evaluate the correlation of inter-individual variation of cyclosporine dosage and blood concentration and CYP3A4 and CYP3A5 polymorphism in renal transplant recipients. Methods:Two hundred and twenty-one renal transplant recipients treated with cyclosporine were genotyped for CYP3A4 rs4646437C>T and CYP3A5 6986G>A using ligase detection reactions. The effects of genetic polymorphisms of CYP3A4 and CYP3A5 on cyclosporine trough concentration (C0/D) and 2 h post-dose concentra-tion (C2/D) during the period of 6 months, 6-24 months and above 24 months after renal transplant were studied. Results:CYP3A5 6986G>A genotype affected C0/D during the period of 6 months, 6-24 months and beyond 24 months (PGA>AA. CYP3A4 rs4646437C>T and CYP3A5 6986G>A genotype affected C2/D during the period above 24 months (PCT>TT and CYP3A5 6986GG>GA>AA. Conclusion: CYP3A5 6986G>A genotype affects C0/D and C2/D of cyclosporine, and CYP3A4 rs4646437 C>T genotype affects C2/D of cyclosporine. The effects of genotypes are varied in different stages.