五酯胶囊和/或金水宝胶囊对CYP3A5基因不表达型特发性膜性肾病患者他克莫司药代动力学的影响  

Effect of Wuzhi capsules and/or Jinshuibao capsules on the pharmacokinetics of tacrolimus in patients with idiopathic membranous nephropathy of CYP3A5 non-expression

作　　者：高菲 徐洋洋[2] 成文娜[2] 张烨[2] 蔺婷婷 魏传梅 GAO Fei;XU Yangyang;CHENG Wenna;ZHANG Ye;LIN Tingting;WEI Chuanmei(School of Pharmacy,Binzhou Medical University,Yantai 264003,Shandong,P.R.China;Department of Pharmacy,Binzhou Medical University Hospital,Binzhou 256603,Shandong,P.R.China)

机构地区：[1]滨州医学院药学院,山东烟台264003 [2]滨州医学院附属医院药学部,山东滨州256603

出　　处：《滨州医学院学报》2022年第1期41-45,共5页Journal of Binzhou Medical University

基　　金：山东省医药卫生科技发展计划(2017WS041);山东省医学会治疗药物监测科研基金(YXH2020ZX054);中国毒理学会临床毒理专项课题(CST2019CT309)。

摘　　要：目的探讨五酯胶囊(WZC)/金水宝胶囊(JSB)对CYP3A5基因不表达型特发性膜性肾病患者他克莫司(TAC)血药浓度、日剂量、血药浓度/日剂量的影响,为优化TAC联合用药方案提供依据。方法收集CYP3A5基因不表达型特发性膜性肾病患者48例,根据用药方案不同分为TAC组(n=6)、TAC+WZC组(n=19)、TAC+JSB组(n=9)、TAC+WZC+JSB组(n=14)。在第8、16、24周后分别比较4组患者TAC血药浓度、日剂量、血药浓度/日剂量。结果治疗第8周时,与TAC组比较,TAC+JSB组患者的TAC血药浓度降低,P<0.05;治疗第16周时,与TAC组比较,TAC+JSB组和TAC+WZC+JSB组患者的TAC血药浓度均降低,P<0.05;治疗第24周时,与TAC组比较,TAC+JSB组和TAC+WZC+JSB组患者的TAC血药浓度均降低,P<0.05。治疗第8周时,与TAC组比较,TAC+JSB组患者的TAC日剂量升高,P<0.05;治疗第16周时,与TAC组比较,TAC+JSB组的TAC日剂量升高,P<0.05,而TAC+WZC+JSB组患者的TAC日剂量降低,P<0.05;治疗第24周时,与TAC组比较,TAC+JSB组的TAC日剂量升高,P<0.05,而TAC+WZC+JSB组患者的TAC日剂量降低,P<0.05。治疗第8周时,与TAC组比较,TAC+JSB组患者的TAC血药浓度/日剂量降低,P<0.01,而TAC+WZC+JSB患者的TAC血药浓度/日剂量升高,P<0.05;治疗第16和24周时,与TAC组比较,TAC+JSB组患者的TAC血药浓度/日剂量降低,P<0.01。结论CYP3A5基因不表达型IM N患者中,JSB可降低TAC血药浓度,加用WZC可增大JSB导致的TAC血药浓度降低程度,合用WZC并不能提高单用TAC时血药浓度。实际工作中应制定切实可行的TAC血药浓度监测与基因检测相辅相成的工作流程,以达到有效、安全和经济的用药目的。Objective To investigate the effects of Jinshuibao capsules(JSB)/Wuzhi capsules(WZC)on whole blood concentration,dosage and whole blood concentration/dosage of tacrolimus(TAC)in patients with IMN of CYP3A5 non-expression,to provide the basis for optimizing TAC combination drug regimen.Methods Forty-eight patients with IMN of CYP3A5 non-expression admitted to our hospital were enrolled in the study and divided into the TAC group(n=6),the TAC+WZC group(n=19),the TAC+JSB group(n=9),and the TAC+WZC+JSB group(n=14).The whole blood concentration(C_(0)),TAC dosage(D)and C_(0)/D were compared among the four groups after 8,16 and 24 weeks.Results At the 8th week of treatment,TAC C_(0) in TAC+JSB group was lower than that in TAC group,P<0.05;At the 16th week of treatment,compared with TAC group,TAC+JSB group and TAC+WZC+JSB group had lower TAC C_(0),P<0.05.0.05;At the 24th week of treatment,compared with TAC group,TAC+JSB group and TAC+WZC+JSB group had lower TAC C_(0),P<0.05.At the 8th week of treatment,the TAC daily dose in TAC+JSB group was higher than that in TAC group,P<0.05;At week 16,compared with TAC group,TAC+JSB group had higher daily TAC dose,P<0.05;The TAC daily dose of TAC+WZC+JSB group decreased,P<0.05;At the 24th week of treatment,the TAC daily dose of TAC+JSB group was higher than that of TAC group,P<0.05;The TAC daily dose of TAC+WZC+JSB group decreased,P<0.05.At the 8th week of treatment,TAC C_(0)/D in TAC+JSB group was lower than that in TAC group,P<0.01.The serum TAC C_(0)/D of TAC+WZC+JSB patients increased,P<0.05;At weeks 16 and 24,TAC C_(0)/D in TAC+JSB group was lower than that in TAC group,P<0.01.Conclusion In patients with IMN of CYP3A5 non-expression,the whole blood concentration of TAC caused by JSB decreased,and the addition of WZC could improve the whole blood concentration of TAC caused by JSB,but the combination of WZC could not improve the whole blood concentration of TAC alone.In practice,it is necessary to establish a feasible work flow of blood drug concentration monitoring and gene dete

关 键 词：特发性膜性肾病 CYP3A5基因不表达型 他克莫司 五酯胶囊 金水宝胶囊 剂量 

分 类 号：R969.2[医药卫生—药理学]