吲达帕胺片在中国健康受试者体内的人体生物等效性研究

A Bioequivalence Study on Indapamide Tablets Versus Reference Preparation in Chinese Healthy Volunteers

目的研究吲达帕胺受试制剂(片剂)和参比制剂(片剂)空腹给药的人体生物等效性。方法采用开放、随机、单剂量、两周期、两序列、交叉试验设计,将纳入的12名健康志愿者随机分为2组,分别口服受试制剂和参比制剂2.5 mg,采用超高效液相色谱串联质谱(UHPLC-MS/MS)技术,建立了快速、简单、灵敏的的分析方法测定人全血中吲达帕胺浓度,用于吲达帕胺片人体生物等效性预试验研究。利用DAS软件计算其药动学参数,评价其生物等效性。结果吲达帕胺受试制剂和参比制剂的主要药动学参数:C_(max)分别为(128.7±19.4)ng/ml和(126.5±19.2)ng/ml;T_(max)分别为(1.5±0.6)h和(1.5±0.5)h;AUC_(0-t)分别为(2163.4±352.4)ng/ml和(2148.5±346.2)ng/ml;AUC_(0-∞)分别为(2241.1±383.8)ng/ml和(2228.4±371.5)ng/ml,相对生物利用度为99.5%±6.2%。结论受试制剂AUC_(0-t)、 AUC_(0-∞)和C_(max)的90%置信区间均在参比制剂相应参数的80.00%~125.00%范围内。方差分析及双单侧t检验结果显示,受试吲达帕胺缓释片与参比吲达帕胺缓释片具有生物等效性。

Objective To study the bioequivalence of indapamide test preparation(tablets) and reference preparation(tablets) administered in the fasting state in human body. Methods An open, randomized, single-dose, two-period,two-sequence and crossover design was adopted. A total of 12 subjects were randomly assigned into two groups and were given a single dose of 2.5 mg test preparation or reference preparation respectively. A rapid, simple and sensitive UHPLC-MS/MS method was developed for determination of indapamide in human blood, which was used in the preliminary study of bioequivalence of Indapamide Tablets in human body. The pharmacokinetic parameters were calculated and the bioequivalence was evaluated by DAS software. Results The main pharmacokinetic parameters of the test preparation and the reference preparation were as follows: Cmax were(128.7±19.4) ng/ml and(126.5±19.2) ng/ml, respectively;T;were(1.5±0.6) h and(1.5±0.5) h;AUC_(0-t) were(2163.4±352.4) ng/ml and(2148.5±346.2) ng/ml;AUC_(0-∞) were(2241.1±383.8) ng/ml and(2228.4±371.5) ng/ml. The results showed that the bioavailability was 99.5 %±6.2 %. Conclusion The 90 % confidence intervals of AUC_(0-t), AUC_(0-∞) and C_(max) of the test preparation were within the ranges of 80.0 %-125.0 % of the corresponding parameters of the reference preparation. The results of ANOVAR and two one-side t-tests show that the test preparation and reference preparation are bioequivalent.