丙泊酚注射液在中国健康志愿者中的药动/药效学研究

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 7 d。受试者在心电、脑电监护的情况下给药,给药前2 min至用药后 15 min 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: C_max 分别为 2.284 和 2.452 mg/L; t_max 分别为4 和 4 min; AUC_0-t 分别为 0.706 和 0.423 mg·h·L^-1; AUC_0-∞ 分别为 0.471 和 0.506 mg·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:BIS_min分别为 51 and 53; AAI_min分别为18 和20; BISAUC_{0-15 min}分别为 373.4 和 342.7; AAIAUC_{0-15 min}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。

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

AIM: Propofol is a widely used intravenous anesthetic agent. Few pharmacokinetic (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 equivalence between two injection formulations of propofol in Chinese healthy volunteers. METHODS: Twenty-four healthy male volunteers were enrolled in a randomized, double-blinded, crossover study, receiving a 2 mg/kg bolus injection of test or reference formulation in two study arms. Plasma propofol concentration was determined by a validated HPLC-Flu method. PD parameters, Bispectral Index (BIS) and A-line ARX Index (AAI), were recorded by EEG monitor till 15 min postdose. In addition, times to onset of and emergence from hypnosis were observed. RESULTS: Twenty-three subjects accomplished the trial. The mean values of C_max, t_max, AUC_0-t, AUC_0-∞ of test and reference formulations were 2.284 and 2.452 mg/L; 4 and 4 min; 0.706 and 0.423 mg·h·L^-1; 0.471 and 0.506 mg·h·L^-1, respectively. The mean values of PD parameters of test and reference formulations were as follows: BIS_min, 51 and 53, respectively; AAI_min, 18 and 20; BISAUC_{0-15 min}, 373.4 and 342.7; AAIAUC_{0-15 min}, 892.5 and 850.5. The 90% CIs for the logarithmic transformations of C_max, AUC_0-t, AUC_0-∞, BISAUC_{0-15 min}, BIS_min, AAIAUC_{0-15 min}, AAI_min (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, respectively) were within the bioequivalence acceptance 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 pharmacodynamic. Both formulations were well tolerated. Therefore, we believe that the two injection formulations of propofol are therapeutic equivalence in Chinese healthy volunteers.