Effect Of CYP3A5 Genetic Polymorphisms And Wuzhi Capsule On The Pharmacokinetics Of Tacrolimus In Patients With Idiopathic Membranous Nephropathy

The First Study:Effect of CYP3A5 Genetic Polymorphisms on the Pharmacokinetics of Tacrolimus in Patients with Idiopathic Membranous NephropathyObjective:To research the effect of CYP3A5 gene polymorphisms on the whole blood trough concentration(C0) of tacrolimus(TAC) in patients with idiopathic membranous nephropathy (IMN),and to predict the optimum initial dosage which was not only getting the best curative effect but also reaching the minimum drug adverse reaction and financial burden.Methods:Sixty patients with idiopathic membranous nephropathy (IMN) 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,GG). At the same time, the author measured the C0 of TAC 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 between 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 (allp<0.05). To reach the same C0, the patients with AA needed 2-3 fold dosage of TAC than GG, and 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:WZC could increase the concentration of TAC in CYP3A5 expressers with IMN,safely and placidly.So it is apparently that TAC combined with WZC could decrease the dosage of TAC and ease the burden of the patients above.The second study:Effect of Wuzhi Capsule on the pharmacokinetics of Tacrolimus in CYP3A5 expressers with Idiopathic Membranous NephropathyObjective:To explore the effect of Wuzhi capsules(WZC) on whole blood concentration of tacrolimus(TAC) and its security and stability in patients with idiopathic membranous nephropathy(IMN) which are CYP3A5 expressers(AA or AG) with the aim of inferring the dosage of TAC.Methods:Sixty-eight CYP3A5 expressers with IMN were divided randomly into two groups:experimental (TAC+WZC+prednison, n=34, lost 2) and control (TAC+prednison, n=34, lost 1).The genotype of CYP3A5were tested by fluorescence in situ hybridization(FISH).Age,sex,genotype,pathologic type,blood pressure (BP),urine protein,serum albumin, sugars, hepatic function and renal function were compared between the two groups before treatment. The Whole blood trough concentration (C0:ng/ml),TAC dosage(D,mg.kg-1.d-1)and C0/D [(ng.ml-1)/(mg.kg-1.d-1)]were compared between the two groups after 8 weeks,16 weeks and 24 weeks. At the same time,the treatment effects and adverse reactions of the two groups were compared and evaluated.Results:The second study:(1)There was no significantly difference (p> 0.05) in baseline data between the two groups before treatment.(2)The Whole blood trough concentration (C0)between the two groups was similar at different visit viewpoints.TAC dosage (D) of experimental group was significantly less(p <0.001)than that of control group and C0/D of experimental group was significantly higher(p<0.001)than that of control group. Referring to the dosage of TAC and C0/D,there were no statistically significant difference (p > 0.05) in experimental group at the different visit viewpoints.The average dosage of TAC in experimental group was (0.037×0.002) mg.kg-1.d-1,which was approximately 60% to the control group.(3)The effective rate and adverse reaction rate were no significantly difference (p>0.05) between the two groups.Conclusions:WZC could increase the concentration of TAC in CYP3A5 expressers with IMN,safely and placidly.So it is apparently that TAC combined with WZC could decrease the dosage of TAC and ease the burden of the patients above.