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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。
OBJECTIVE: Propofol is a short-acting intravenous anesthetic widely used clinically. In this paper, the pharmacokinetics and pharmacodynamic characteristics of propofol were studied to evaluate the therapeutic equivalence of domestic propofol injection and imported products. Methods: Randomized, double-blind, two-period, crossover design. A total of 24 subjects were enrolled in the study, and were given test preparations or control drugs at different cycles, with an elution period of 7 days. Subjects were administered with ECG and EEG monitoring. The scores of BIS, AAI, heart rate, respiration, blood pressure and blood were recorded in real time from 2 minutes before treatment to 15 minutes after treatment. Oxygen saturation, recording anesthesia time. Plasma drug concentration was determined by HPLC-Flu method. Adverse events were recorded during the experiment. RESULTS: A total of 23 subjects completed the trial. The main pharmacokinetic parameters of the test and reference formulations were as follows: Cmax 2.284 and 2.452 mg / L, tmax 4 and 4 min, respectively; AUC0-t 0.706 and 0.423 mg.hL-1; AUC0-∞ 0.471 and 0.506 mg.hL-1, respectively. The relative bioavailability between the two formulations was 93.1%. The main pharmacodynamic parameters of the test formulation and the reference formulation were as follows: BISmin 51 and 53, AAImin 18 and 20 respectively, BISAUC 0-15min 373.4 and 342.7, AAIAUC 0-15min 892.5 and 850.5, respectively. Conclusion: The domestic propofol injection and imported products have equivalent pharmacokinetics and pharmacodynamics, and the safety is good. Therefore, both of them are considered to be equivalent in treatment.