Population pharmacokinetics of remifentanil in adult patients undergoing elective major abdominal sur-gery
- VernacularTitle:成人患者瑞芬太尼群体药代动力学初步研究
- Author:
Qiang WANG
;
Fang BAO
;
Lijun LIU
;
Qinfang GUI
;
Zhengliang MA
- Publication Type:Journal Article
- Keywords:
Remifentanil;
Population pharmacokinetics;
Nonlinear mixed effect model (NONMEM)
- From:
The Journal of Clinical Anesthesiology
2014;(12):1156-1160
- CountryChina
- Language:Chinese
-
Abstract:
Objective The aim of this study was to explore possible pharmacokinetic factors and develop a population pharmacokinetic model for remifentanil in adult patients.Methods Eleven healthy patients,undergoing elective major abdominal surgery,aged 25 to 86 years,received random-ly remifentanil 0.3μg·kg-1 ·min-1 (group R3),or 0.6μg·kg-1 ·min-1 (group R6).Frequent ar-terial blood samples were drawn according to predetermined time and assayed for remifentanil concen-tration.Nonlinear mixed-effects modeling (NONMEM)was used to evaluate the time courses of the measured concentrations.The covariates include age,bodyweight (WT),gender,lean body mass (LBM),body mass index (BMI)and body surface area (BSA).Results The pharmacokinetic data of remifentanil were well described using a three-compartment linear model with first-order elimination from the central compartment.Forward analysis showed that age,height and body mass index (BMI) does not affect the pharmacokinetic parameters,which are contrast with body weight,lean body mass (LBM),body surface area (BSA)and gender;further analysis demonstrated only a significant effect of body weight on remifentanil systemic clearance (CL)and volume of the central compartment (V). For typical 60 years patients,PK parameters were:V1 =7.64 L,V2 =4.81 L,V3 =4.34 L,CL1 =2.74 L/min,CL2 = 0.738 L/min,CL3 = 0.0905 L/min.Conclusion The pharmacokinetics of remifentanil is consistent with its rapid elimination by blood and tissue esterase in Chinese patients. The systemic clearance and volume of distribution of central compartment increases with body weight in the population and the range of covariates studied,which suggests that a patient with greater body weight needs a greater initial dose and maintenance infusion rate higher to obtain a stable plasma con-centrations and clinical effects.
