摘要
评价两种环孢素软胶囊(受试制剂和参比制剂)在健康中国人体内的生物等效性。建立测定人全血中环孢素A的高效液相色谱-紫外(HPLC-UV)检测法,并进行方法学验证,采用随机双交叉自身对照试验设计,24名男性健康受试者分别口服受试制剂和参比制剂400mg后,测定环孢素A的血药浓度,计算药动学参数,评价两制剂的生物等效性。环孢素软胶囊(受试制剂)和环孢素软胶囊(参比制剂)中环孢素A主要的药动学参数如下:消除半衰期T1/2分别为(10.114±6.329)h和(9.717±4.076)h,达峰浓度Cmax分别为(2 021.235±298.581)ng.ml-1和(1 992.192±286.923)ng.ml-1,达峰时间Tmax分别为(1.729±0.361)h和(1.813±0.323)h;药时曲线下面积AUC0→t分别为(9 824.811±1 633.026)ng.h.ml-1和(10 316.514±1 395.955)ng.h.ml-1。以AUC0→t计算,环孢素软胶囊的相对生物利用度为(97.2±22.1)%。结果表明两制剂在健康中国人体内具有生物等效性。
This paper is aimed to study the bioavailability and bioequivalence of Cyclosporin Soft Capsules（test preparation and reference preparation） in Chinese healthy volunteers.A high performance liquid chromatography-ultraviolet（HPLC-UV） method for determining the concentration of Cyclosporin A in human whole blood was developed and methodological validated.In accordance with the randomized two-period self crossover study,24 volunteers received a single oral dose of 400 mg of test preparation or reference preparation.Multiple blood samples were collected post dose and then the concentration of Cyclosporin A in human whole blood samples was determined using the validated assay.The pharmacokinetic parameters including AUC0-t,Cmax,Tmax,and T1/2 were calculated using the non-compartmental method.The bioequivalence of the two preparations was evaluated.After receiving single dose of 400 mg of Cyclosporine A,the pharmacokinetic parameters of T1/2,Cmax,Tmax,and AUC0-t of Cyclosporin A were（10.114±6.329）h and（9.717±4.076）h,（2 021.235±298.581）ng·ml-1 and（1 992.192±286.923）ng·ml-1,（1.729±0.361）h and（1.813±0.323）h,（9 824.811±1 633.026）ng·h·ml-1 and（10 316.514±1 395.955）ng·h·ml-1 for test preparation and reference preparation,respectively.The statistical results suggested that these parameters were comparable between the two preparations.The results showed that the test preparation was bioequivalent with the reference preparation in healthy volunteers.
出处
《生物医学工程学杂志》
EI
CAS
CSCD
北大核心
2012年第2期311-314,331,共5页
Journal of Biomedical Engineering
关键词
环孢素A
高效液相色谱
药动学
生物等效性
Cyclosporin A
High performance liquid chromatography（HPLC）
Pharmacokinetic
Bioequivalence
