患者静脉输注依托咪酯的群体药代动力学

Population pharmacokinetics of intravenous etomidate infusion in adult patients

目的评价患者静脉输注依托咪酯的群体药代动力学。方法择期全麻患者29例，年龄25～82岁，以60μg·kg^-1·min^-1速率持续静脉输注依托咪酯，直至脑电双频谱指数值〈40。于输注依托眯酯前、持续输注1、3、5min及停药即刻、停止输注后1、3、5、7、10、20、30、45、75、120、180、240、300和360min时取桡动脉血样，测定血浆药物浓度。采用NONMEM软件建立依托咪酯群体药代学模型，分析年龄、身高、体重等协变量的影响。参数个体间变异性和残差变异性分别采用指数模型和相加误差模型描述，模型改善的统计学标准依据目标函数判断。结果依托咪酯药代学适合用三室模型描述，年龄是系统清除率CL1的影响因素。依托咪酯药代学参数典型值为：V1=4．7L，V2=11L，V3=123L，CL1=1．28—0．0119×[年龄（岁）-55]L／min，ck=1．25L／min和ck=1．08L／min。输注时间敏感性半衰期随年龄和稳态输注时间的增加而升高（P〈0．05）。结论依托咪酯药代学适合用三室模型描述，年龄因素影响系统清除率。

Objective To determine the population pharmacokinetics of intravenous etomidate infusion in adult patients. Methods Twenty-nine ASA I or 11 patients of both sexes aged 25-82 yr weighing 45-80 kg received contant-rate infusion of etomidate at 60μg·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： VI = 4.7 L, Vz = 11 L, V3 = 123 L, CL1 = 1.28 - 0.0119 x （Age （yr） - 55） L/min, CL2 = 1.25 L/min and CL3 = 1.08 L/min respectively. Cont- ext-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）.