吲哒帕胺软胶囊在人体内的相对生物利用度  

Relative bioavailability of indapamide soft capsules in healthy volunteers

作　　者：孙荣梅[1] 杭太俊[2] 赵卫[2] 宋敏[2] 

机构地区：[1]中国药科大学高等职业技术学院,镇江212003 [2]中国药科大学药物分析室,南京210009

出　　处：《中国临床药学杂志》2006年第6期360-363,共4页Chinese Journal of Clinical Pharmacy

摘　　要：目的建立液-质联用内标法测定人全血中吲哒帕胺的浓度，并研究吲哒帕胺软胶囊在健康人体内的相对生物利用度。方法20名健康受试者随机分为2组进行单剂量双交叉试验。受试者单剂量口服吲哒帕胺软胶囊（试验制剂）或吲哒帕胺片（参比制剂）5mg，采集静脉全血样本，经乙醚提取后，用液-质联用法测定全血中吲哒帕胺的血药浓度经时过程，并用3P97程序计算主要药动学参数。结果LC—MS／MS法测定全血中吲哒帕胺在10．0—400μg·L^-1范围具有良好线性响应，检测限浓度为0．1μg.L^-1。测得试验制剂和参比制剂的主要药动学参数：tmax分别为（1．1±0．6）、（2．6±1．4）h；pmax分别为（371．5±88．4）、（289．84±58．4）μg.L^-1；t1／2分别为（20．54±3．4）、（20．44±3．8）h；AUC0→48h分别为（55164±541）、（55234±532）μg·h·L^-1。ANOVA表明试验制剂与参比制剂主要药动学参数之间差异无统计学意义；相对生物利用度为（100．34-10．1）％。结论酢MS／MS法测定全血中吲哒帕胺的血药浓度灵敏度高、专属性好、定量准确，试验制剂与参比制剂具有生物等效性。A/M To develop a LC-MS/MS method for the study on bioequivalenee of indapamide soft capsules in healthy volunteers. METHODS A single oral dose of 5 mg indapamide of test soft capsules or reference tablets were given to 20 healthy male volunteers in an open randomized two-way cross-over design. The concentrations of indapamide in whole blood samples were determined by a validated LC-MS/MS method after diethyl ether extraction. The pharmacoki- netic parameters were calculated by 3P97 software. RESULTS The calibration of the LC-MS/MS analysis was linear in the range of 10.0 - 400μg.L^- 1 with the limit of quantitation of 0.1μg.L^- 1. The main pharmacokinetic parameters of indapsmide were as follows： tmax（ 1.1 ± 0.6）h and （2.6 ± 1.4）h, pmax（371.5 ± 88.4）μg. L^-1 and （289.8 ± 58.4）μg.L^-1,t1/2（20.5 ± 3.4）h and （20.4± 3.8）h, AUC0→48h（5 516± 541）μg.h.L^-1 and （5 523±532） μg.h.L^-1 for test soft capsules and reference tablets, respectively. The results showed that there was no significant difference between two preparatiom. The relative bioavailability was （ 100.3 ＋ 10.1） %. CONCLUSION The LC-MS/MS method is selective, sensitive and accurate for the determination of indapamide in whole blood samples. The results of two one-sided ttest show that the test and reference preparations are bioequivalent.

关 键 词：吲哒帕胺 生物等效性 LC-MS/MS法 

分 类 号：R96[医药卫生—药理学]