上海交通大学学报（医学版）

上海交通大学学报（医学版）

• 论著（临床研究） • 上一篇    下一篇

小儿依托咪酯短期输注后的群体药代动力学特点及影响因素

魏 嵘1，王 春1，张赛吉1，刘珺珺1，林 琳2   

  1. 上海交通大学 1.附属儿童医院麻醉科， 上海 200040； 2.医学院附属上海儿童医学中心麻醉科， 上海 200127
  • 出版日期:2014-06-28 发布日期:2014-06-30
  • 作者简介:魏 嵘（1968—）， 男， 副主任医师， 硕士; 电子信箱: weir@shchildren.com.cn。
  • 基金资助:

    国家自然科学基金（81202597）；上海市卫生局基金（20124292）；上海交通大学医学院科技基金（12XJ10074）

Characteristics of population pharmacokinetics and influence factors after short-term injection of etomidate to children

WEI Rong1, WANG Chun1, ZHANG Sai-Ji1, LIU Jun-Jun1, LIN Lin2   

  1. 1.Department of Anesthesiology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200040, China; 2.Department of Anesthesiology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
  • Online:2014-06-28 Published:2014-06-30
  • Supported by:

    National Natural Science Foundation of China, 81202597；Shanghai Municipal Health Bureau Foundation, 20124292；Shanghai Jiao Tong University School of Medicine Foundation,12XJ10074

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摘要：

目的 探索短期输注依托咪酯后的药代动力学特点及影响因素，并建立群体药代动力学模型。方法 11例拟在全身麻醉下行择期手术的ASA分级Ⅰ～Ⅱ级患儿，静脉持续输注依托咪酯60 μg·kg-1·min-1直至双频谱指数（BIS）值降低到50以下。按照预先设定的时间点抽取动脉血标本并测定依托咪酯血浆浓度。采用非线性混合效应模型建立依托咪酯群体药代动力学模型，分析年龄、身高、体质量等协变量对药代动力学参数的影响。结果 起始分析提示一室、二室和三室模型的目标函数值分别为61、-63和-77，小儿依托咪酯药代动力学最适合用三室模型描述，基于体质量的异速生长模型拟合后目标函数进一步减少，未发现有显著影响药代动力学的其他协变量。群体药代动力学参数典型值为：V1=6.53×(体质量/70)(L), V2=12.4×(体质量/70)(L)，V3=27.3×(体质量/70)(L), Cl1=1.23×(体质量/70)0.75(L/min), Cl2=1.42×(体质量/70)0.75 (L/min)和Cl3=0.35×(体质量/70)0.75。结论 年龄不影响依托咪酯的药代动力学，提示其代谢途径出生后即已成熟；体质量以异速生长方式影响依托咪酯的药代动力学，提示较小体质量的儿童单位体质量需要更高的输注剂量和速度。

关键词: 依托咪酯, 小儿, 群体药代动力学, 异速生长

Abstract:

Objective To explore the characteristics of pharmacokinetics and influence factors after short-term injection of etomidate and to establish the population pharmacokinetics model. Methods Eleven pediatric patients with ASA Ⅰ-Ⅱ who scheduled to undergo elective surgeries under general anesthesia were selected. Etomidate of 60 μg·kg-1·min-1 was intravenously injected until the bispect ral index (BIS) value was below 50. The arterial blood samples were drawn at scheduled time points and the plasma concentration of etomidate was detected. Nonlinear mixed-effect model was adopted to establish the population pharmacokinetics model of etomidate. The effects of covariates (such as the age, height, and body mass, etc.) on pharmacokinetic parameters were analyzed. Results Initial analysis showed that the objective function values were 61, -63, and -77 for the one-compartment model, two-compartment model, and three-compartment model, respectively. The three-compartment model was most suitable for describing the pharmacokinetics of etomidate for children. The number of target functions further decreased after the body mass based allometric model was fitted. No other covariates that could significantly affect the pharmacokinetics were found. The typical values of population pharmacokinetic parameters were: V1=6.53×(WT/70)(L), V2=12.4×(WT/70)(L), V3=27.3×(WT/70)(L), Cl1=1.23×(WT/70)0.75(L/min), Cl2=1.42×(WT/70)0.75 (L/min), and Cl3=0.35×(WT/70)0.75. Conclusion Age does not affect the pharmacokinetics of etomidate, which suggests the metabolic pathway is mature at birth. The allometric effect of body weight on the pharmacokinetics of etomidate shows that for children with smaller body masses, their injection dose and rate of unit body mass should be higher.

Key words: etomidate, pediatric, population pharmacokinetics, allometrics