RESUMO
Objective To determine the population pharmacokinetics of intravenous etomidate infusion in adult patients.Methods Twenty-nine ASA Ⅰ or Ⅱ patients of both sexes aged 25-82 yr weighing 45-80 kg received contant-rate infusion of etomidate at 60 μg· kg-1 · min-1 until BIS value dropped to ≤ 40.Arterial blood samples were obtained from radial artery for determination of plasma etomidate concentration before,at 1,3,5 min of continuous etomidate infusion and at 1,3,5,7,10,20,30,45,75,120,180,240,300 and 360 min after termination of etomidate infusion.Population pharmacokinetic model was established by using the software package NONMEM.Population pharmacokinetic parameters were calculated according to etomidate concentrations and covariates including age,height,bodyweight,sex,liver-kidney function etc.using software package NONMEM.Results Pharmacokinetics of etomidate was best described by a three-compartment pharmacokinetic model with age as a covariate affecting systemic clearance (CL1).The typical parameters were:V1 =4.7 L,V2 =11 L,V3 =123L,CL1 =1.28-0.0119 × (Age (yr)-55) L/min,CL2 =1.25 L/min and CL3 =1.08 L/min respectively.Context-sensitive half-time increased with age and steady-state infusion time.Conclusion Pharmacokinetics of etomidate is best described by a three-compartment pharmacokinetic model with age as a covariate affecting systemic clearance (CL1).