Population pharmacokinetics of propofol administered by TCI in Chinese / 中华麻醉学杂志

ABSTRACT

Obuective To assess the population pharmacokinetic parameters and analyze thecharacteristics of pharmacokinetics of propofol given by target-controlled infusion (TCI) in Chinese using anoulinear mixed effect model (NONMEM) program. Methods Sixty-one ASA Ⅰ-Ⅱ patients (26 male, 35female) aged 18-64yr, weighing 41-83kg undergoing elective operation under general anesthesia were studied. TheTCI system consisted of (1 ) Stel pump Software 1 .07 designed by Coetzee, (2) cable R232 connector, (3)Graseby 3500 infusion pump, (4 ) pharmacokinetic parameters developed by Tackley. The patients werepremedicated with intramuscular phenobarbital sodium 1-2 mg?kg~(-1) and atropine 0. 5 mg. Anesthesia was inducedwith TCI of propofol. Target plasma concentration of propofol was set at 3?g?ml~(-1). Fentanyl 2?g?kg~(-1) andvecuronium 0. 1mg?kg~(-1) were given i. v. when the patients lost consciousness. TCI of propofol lasted 60 min. 976blood samples were obtained before induction of anesthesia and at 2, 5, 10, 20, 30, 40, 50, 60, 62. 5, 65, 70,75, 80, 85, 90 min ther TCI was started for determination of plasma propofol concentration by gas-chromatography-mass spectrometry (GC-MS). Population pharmacokinetic parameters were assessed and thecharacteristics of the pharmacokinetic profile was analyzed using NONMEM program. Results The pharmacokineticprofile of propofol given by TCI in Chinese was best described by an open two-compartment model. Thepharmacokinetic parameters for the final model K_(10) was 0.111, K_(12) 0 .064 and K_(21) 0 .023 min~(-1); V_1 was 0 .205and V_2 0.404 L?kg~(-1); CL_1 was 22 .76 and CL_2 13 .24 ml?min~(-1). The estimated concentrations were well correlatedwith the measured concentrations in the final model. Weight was found to covariate significandy with V_1 and CL_1and age with K_(21). However gender had no significant effect on pharmacokinetic parameters.Conclusion Thepopulation pharmacokinetic profile of propofol administered by TCI in Chinese can be well described by an open two-compartment model. The volume of central compartment was smaller and the inter-compartmental transfer ratefrom central compartment to peripheral compartment was faster in Chinese.