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

Abstract

Abstract: 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.

Key words: Propofol, Therapeutic equivalence, Pharmacokinetics, Pharmacodynamics, HPLC-Flu, Healthy volunteer

CLC Number:

R969.1

CHEN Lin-yao, ZHOU Xing-chen, GUO Xin, SU Tao, CHENG Ze-neng. Pharmacokinetics/pharmacodynamics evaluation of two injection formulations of propofol in Chinese healthy volunteers[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(11): 1249-1257.

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