Prediction of initial dosage of tacrolimus in patients with idiopathic membranous nephropathy by testing CYP3A5 genetic polymorphisms / 中华肾脏病杂志

ABSTRACT

Objective To explore the effect of CYP3A5 gene polymorphisms on the whole blood trough concentration (C0) of tacrolimus (TAC) in patients with idiopathic membranous nephropathy to identify an economical and optimal initial dosage delivering the best curative effect with minimum drug adverse reaction.Methods Sixty patients with idiopathic membranous nephropathy were enrolled in this study.The CYP3A5 genotype was tested by fluorescence in situ hybridization (FISH).According to CYP3A5 genotype, the patients were divided into three groups (AA, AG, and GG).At the same time, the C0 of TAC was measured by enzyme multiplied immunoassay technique (EMIT).C0 of TAC, daily dosage of TAC and the concentration/dose(C0/D) ratio of TAC were detected after taking medicine at 8, 12, 16 and 24 weeks respectively, so as to corroborate the relation between CYP3A5 gene polymorphisms and the dosage of TAC.Results The oral TAC dosage had great variation among individuals.The occurrence of the CYP3A5 genetic polymorphisms (A6986G) designated as G was 53.33％.D and C0 were significantly different at 8, 12, 16 and 24 weeks respectively (all P ＜ 0.05).To reach the same C0, the patients with AA needed 2-3-fold dosage of TAC than GG;and those with AG needed 1-2-fold dosage of TAC than GG.After 24-week treatment, the effective rate of AA group was markedly lower than AG and GG (16.67％ vs 81.25％, 16.67％ vs 87.50％, all P ＜ 0.001).Among CR, PR and NR, there were no significantly difference on C0 or C0/D of TAC (P ＞ 0.05).Conclusions CYP3A5 genotypes are correlated with blood concentration of TAC.CYP3A5 genotyping may be a new approach to predict the optimal initial dosage of tacrolimus in idiopathic membranous nephropathy.