吲达帕胺片体外溶出行为及在健康人体生物等效性研究

Study on the in vivo and Bioequivalence of Indapamide Tablets in Health Volunteers

分别以4种介质(水、pH 1.2盐酸溶液、pH 4.5醋酸盐缓冲溶液、pH 6.8磷酸盐缓冲溶液)为溶出介质,采用HPLC法测定吲达帕胺片在4种溶出介质中的溶出曲线,通过相似因子f_(2)对自制制剂及参比制剂的溶出行为进行比较;选择24名健康受试者进行空腹、开放、随机、单次给药、两序列、两周期的交叉试验,采用LC-MS/MS法测定吲达帕胺的血浆浓度;受试制剂和参比制剂的AUC_(0-t)分别为(2368.76±483.17) ng·h/mL和(2 371.62±463.78) ng·h/mL,AUC0-∞分别为(2472.71±554.94) ng·h/mL和(2457.15±511.21)ng·h/mL,Tmax分别为(2.19±1.21) h和(1.68±0.55)h,Cmax分别为(139.541±27.345) ng/mL和(145.392±23.911)ng/mL。受试制剂和参比制剂的几何均值比符合生物等效性要求,确定受试制剂和参比制剂生物等效。

To study the in vitro dissolution behavior of indapamide tablets and the pharmacokinetic process in healthy humans,complete the in vitro and in vivo correlation evaluation and evaluate its bioequivalence.Using water,pH1.2 hydrochloric acid solution,pH 4.5 acetate buffer solution,and pH 6.8 phosphate buffer solution as dissolution media,the dissolution profiles of indapamide tablets in 4 dissolution media were determined by high performance liquid chromatography.Dissolution was evaluated by a comparison of the dissolution profiles using the similarity factor f_(2).24 healthy subjects orally take the test preparation on an empty stomach and 24 healthy subjects orally take the reference preparation on an empty stomach,and use Liquid chromatography tandem mass spectrometry to determine the blood drug concentration.AUC-of the test preparation and that of the reference preparation were(2368.76±483.17)ng·h/mL and(2371.62±463.78)ng·h/mL respectively;AUC_(0-t)of the test preparation and that of the reference preparation were(2472.71±554.94)ng·h/mL and(2457.15±511.21)ng·h/mL;Tmax of the test preparation and that of the reference preparation were(2.19±1.21)h and(1.68±0.55)h;Cmax of the test preparation and that of the reference preparation were(139.541±27.345)ng/mL and(145.392±23.911)ng/mL.The 90%Cls of the geometric mean value ratios of Cmax,AUCo-and AUCo-were all fell into the bioequivalence range and the bioequivalence of the test preparation and the reference preparation is determined.