丙泊酚注射液在中国健康志愿者中的药动/药效学研究(英文)

Pharmacokinetics/pharmacodynamics evaluation of two injection formulations of propofol in Chinese healthy volunteers

目的:丙泊酚是临床上广泛使用的短效静脉麻醉药,本文通过研究丙泊酚的药动学和药效学特征,从而评价国产丙泊酚注射液与进口产品的治疗等效性。方法:采用随机、双盲、两周期、交叉试验设计。共入组受试者24名,于不同周期分别给予试验制剂或对照药,周期间的洗脱期为7d。受试者在心电、脑电监护的情况下给药,给药前2min至用药后15min实时记录脑电双频指数(BIS值)、听觉诱发电位指数(AAI)、心率、呼吸、血压、血氧饱和度,记录麻醉时间。采用HPLC-Flu法测定血浆药物浓度。试验过程中记录不良事件。结果:共23名受试者完成本试验,试验制剂与参比制剂的主要药动学参数如下:Cmax分别为2.284和2.452mg/L;tmax分别为4和4min;AUC0-t分别为0.706和0.423mg.h.L-1;AUC0-∞分别为0.471和0.506mg.h.L-1。两制剂间的相对生物利用度为93.1%。试验制剂与参比制剂的主要药效学参数如下:BISmin分别为51and 53;AAImin分别为18和20;BISAUC0-15min分别为373.4和342.7;AAIAUC0-15min分别为892.5和850.5。结论:国产丙泊酚注射液与进口产品在药动学及药效学均具有等效性,且安全性良好,故认为二者具治疗等效性。

AIM：Propofol is a widely used in travenous anesthetic agent. Few pharmacokinet- ic （PK） and pharmacodynamic （PD） information of propofol is available in a Chinese population. The aim of the study is to evaluate PK and PD characteristics, assessing the therapeutic equiva- lence between two injection formulations of propofol in Chinese healthy volunteers. METH ODS：Twenty-four healthy male volunteers were enrolled in a randomized, double-blinded, cross- over study, receiving a 2 mg/kg bolus injection of test or reference formulation in two study arms. Plasma propofol concentration was deter mined by a validated HPLC-Flu method. PD pa- rameters, Bispectral Index （BIS） and A-line ARX Index （AAI）, were recorded by EEG mo nitor till 15 min postdose. In addition, times to onset of and emergence from hypnosis were ob served. RESULTS： Twenty-three subjects ac complished the trial. The mean values of C t AUC0-,, AUC0-∞ of test and reference for mulations were 2. 284 and 2. 452 mg/L 4 and 4 mini 0. 706 and 0. 423 mg · h · L-1 0. 471 and0.506 mg·h· L -1, respectively. The mean values of PD parameters of test and reference formulations were as follows. BISon,, 51 and 53, respectively ; AAImin, 18 and 20 ; BI SAUC0-15 min, 373. 4 and 342. 7 ; AA- IAUC0-15 min, 892.5 and 850.5. The 90% CIs for the logarithmic transformations of C AUC0-t, AUC0-∞ , BISAUC0-15 rain, BlSmin, AAIAUC0 l5 min, AAImin （0. 795 - 0. 999, 0. 838 -0.985, 0.861-0.989, 1.023-1.151, 0.865 -1.025, 0.999-1.099, 0.826-1.008, respec- tively） were within the bioequivalence accept- ance limits. No serious adverse events occurred in the trial. CONCLUSION. Results indicated that no significant difference was found between test and reference formulations of＇propofol in the aspects of pharmacokinetic and pharmacodyna- mic. Both formulations were well tolerated. Therefore, we believe that the two injection for mulations of propofol are therapeutic equivalence in Chinese healthy volunteers.