丙泊酚中/长链脂肪乳注射液的生物等效性和药效学研究

Bioequivalence and pharmacodynamics study of propofol medium/long chain fat emulsion injection

目的评价2种丙泊酚中/长链脂肪乳注射液在中国健康受试者空腹状态下的生物等效性和药效。方法按单中心、单剂量、空腹、随机、双盲、两制剂、两周期、交叉设计。入组36例志愿者,随机交叉单次静脉滴注(30μg·kg^(-1)·min^(-1),连续输注30 min)2种丙泊酚制剂,用LC-MS/MS法测定血浆中丙泊酚的药物浓度,用WinNonLin软件计算药代动力学参数,用心电监护仪测定脑电双频指数(BIS)。结果健康志愿者单次静脉滴注丙泊酚受试制剂和参比制剂后,主要药代动力学参数如下:C_(max)分别为(523.89±149.54)和(507.60±132.97)ng·mL^(-1),AUC_(0-t)分别为(419.98±83.41)和(422.26±83.62)ng·mL^(-1)·h,AUC_(0-∞)分别为(444.13±90.09)和(448.18±90.05)ng·mL^(-1)·h,2种制剂的AUC_(0-t)、AUC_(0-∞)和C_(max)经对数转换后90%置信区间分别为96.29%~102.64%,95.89%~102.24%和96.68%~108.93%。药效学参数BIS_(AUC 0-0.5 h)和BIS_(min)经对数转换后90%置信区间分别为100.23%~102.62%和101.24%~111.96%。结论静脉滴注2种丙泊酚中/长链脂肪乳注射液在中国健康志愿者体内具有生物等效性,药效基本一致,且安全、可耐受。

Objective To evaluate the bioequivalence and efficacy of two propofol medium/long chain fat emulsion injections under fasting conditions in healthy Chinese subjects.Methods This was a single-center,single dose,fasting,randomized,double blind,two-preparation,two-period,crossover design.A total of 36 subjects were given single intravenous infusion(30μg·kg^(-1)·min^(-1),continuous infusion for 30 minutes)of test and reference propofol formulations.The concentrations of propofol medium/long chain fat emulsion injections in plasma were determined by LC-MS/MS method.The pharmacokinetic parameters were calculated by WinNonlin,along with bispectral index(BIS)was measured by electrocardiograph monitor.Results The main pharmacokinetic parameters of test and reference preparations of propofol medium/long chain fat emulsion injections were as follows:C_(max) were(523.89±149.54)and(507.60±132.97)ng·mL^(-1),AUC_(0-t) were(419.98±83.41)and(422.26±83.62)ng·mL^(-1)·h,AUC_(0-∞)were(444.13±90.09)and(448.18±90.05)ng·mL^(-1)·h.The 90%CIs for AUC_(0-t),AUC_(0-∞)and C_(max) were 96.29%-102.64%,95.89%-102.24%and 96.68%-108.93%.The 90%CIs of the pharmacodynamic parameters BIS_(AUC 0-0.5 h) and BIS_(min) were 100.23%-102.62%and 101.24%-111.96%,respectively.Conclusion The exposures were equivalent between two propofol medium/long chain fat emulsion injections administered in Chinese healthy subjects,and the efficacy is basically the same,safe and tolerable.