五酯胶囊对CYP3A5基因表达型特发性膜性肾病他克莫司药代动力学影响的初步探索  

Effect of wuzhi capsule on the pharmacokinetics of tacrolimus in patients with Idiopathic membranous nephropathy of CYP3A5 expression

作　　者：杨敏[1] 刘云启[1] 魏传梅[2] 张晓敏[1] 于鹏飞[2] 孙绍伟[2] 

机构地区：[1]滨州医学院附属医院肾内科,山东滨州256600 [2]滨州医学院附属医院药学科,山东滨州256600

出　　处：《国际泌尿系统杂志》2016年第2期223-228,共6页International Journal of Urology and Nephrology

基　　金：山东省药学会临床药学奥赛康中青年科研资助项目（Sapa-ask-2014-03）

摘　　要：目的 分析五酯胶囊（wuzhi capsules,WZC）对CYP3A5基因表达型特发性膜性肾病（idiopathic membranous nephropathy,IMN）患者他克莫司（tacrolimus,TAC）药代动力学指标的影响程度,初步探索此类患者联用WZC后TAC的用药剂量.方法 2013年7月至2015年3月本院肾内科住院经肾穿刺病理活检诊断为IMN,荧光染色原位杂交技术（fluorescence in situ hybridization,FISH）检测CYP3A5基因分型均为CYP3A5基因表达型（即AA、AG）的患者68例,随机数字表分为治疗组（WZC＋ TAC）与对照组（TAC）,比较两组患者治疗开始8周、16周、24周时TAC用药剂量D[mg·（kg·d）^-1]、全血谷浓度C0 （ng/mL）、全血谷浓度与用药剂量的比值C0/D[（ng/mL）/（mg·（kg·d）^-1）],并记录治疗24周两组患者有效率、不良反应发生率.结果 治疗开始8周、16周、24周的各访视点上,两组患者的C0差异无统计学意义（P＞0.05）;组间比较：治疗组的D较对照组显著降低（P ＜0.001）,C0/D较对照组显著升高（P＜0.001）;两组患者组内比较时不同访视点D、C0/D的差异无统计学意义（P＞0.05）,治疗组TAC的平均用药剂量为（0.037±0.002）mg·（kg·d）^-1,约为对照组平均用药剂量的60％.治疗24周,两组患者的治疗有效率以及不良反应发生率的差异无统计学意义（P＞0.05）,但治疗组的有效率较对照组有所升高.结论 WZC可平稳、安全的显著提高CYP3A5基因表达型IMN患者TAC全血谷浓度,进而减少用药剂量、减轻患者的经济负担,为其临床推广创造条件.Objectives 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） of CYP3A5 expression（AA or AG） with the aim of inferring the dosage of TAC.Methods Sixty-eight CYP3A5 expression 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 CYP3A5 were 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 dosageD [mg· （kg · d）^-1）] and C0/D [（ng/mL/mg · （kg · d）^-1）] were compared between the two groups after 8,16 and 24 weeks.At the same time,the treatment effects and adverse reactions of the two groups were compared and evaluated.Results ①There was no significantly difference（P 〉0.05） in baseline data between the two groups before treatment.②The 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· d）^-1,which was approximately 60% to the control group.③The 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 th

关 键 词：肾疾病 免疫抑制剂 药代动力学 

分 类 号：R692[医药卫生—泌尿科学]