Evaluation of population pharmacokinetic parameters for Chinese using NONMEN program
- VernacularTitle:国人异丙酚群体药代动力学参数
- Author:
Yuhong LI
;
Jianzhong RUI
;
Yonggang ZHOU
- Publication Type:Journal Article
- Keywords:
Propofol;
Pharmacokinetics;
Age groups;
Body weight
- From:Chinese Journal of Anesthesiology
1994;0(03):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To assess the population pharmacokinetic parameters for propofol for Chinese surgical patients using a nonlinear mixed- effect model (NONMEN) program and qualitatively analyze the effects of gender, age and body weight.Methods Seventy-six ASA I - II patients(37 male,39 female) ,aged 17-77 years weighing 39-86 kg. Undergoing elective surgery were studied. The patients were premedicated with intramuscular sodium luminal 0.1 g and scopolamine 0.3 mg. Radial artery was cannulated for blood pressure monitoring and blood sampling. BIS, AEPindex, EGG, BP, PET CO2 and SpO2 were continuously monitored during operation. Anesthesia was induced and maintained with propofol and fentanyl. A loading dose of fentanyl 3 ?g? kg-1 was given iv followed by infusion at 2 ?g ? kg -1? h-1 until 30 min before the end of surgery. Propofol 1 -2.5 mg ?kg -1 was given iv over 0.5-4 min followed by infusion at 3-8 mg ? kg-1? h-1 until the end of surgery. When the patient was unconscious intubation was facilitated with vecuronium 0.1 mg? kg-1 . Blood samples were obtained before propofol and 2-120 min during propofol infusion and 2-600 min after discontinuation of propofol infusion for determination of blood propofol concentration. 1 439 blood samples were analyzed using NONMEM program. Interindividual and intraindividual variability was estimated for clearance and volume of distribution. The effects of age, body weight and gender were investigated. Results The pharmacokinetics of propofol in Chinese patients was best described by a three-compartment pharmacokinetic model . Body weight was found to be a significant factor affecting the two inter-compartmental clearances and the volume of the central compartment. The shallow and deep peripheral compartments remained constant for all individuals. For a 60 kg adult these parameters were estimated to be 1.56 L?min-1, 0.737 L?min-1 , 0.360L?min-1 ,12.1 L,43 L,213 L,respectively. For elderly patients, the clearances and volume of central compartment decreased with increasing age. Conclusions The pharmacokinetics of propofol in Chinese patients can be well described by a standard three-compartment pharmacokinetic model. Age and body weight can affect the parameters of the pharmacokinetic model. Pharmacokinetics adjusted to the individual patient should improve the precision of TCI system.
