中国患者靶控输注舒芬太尼的药代动力学两阶段分析。

Two-stage analysis of pharmacokinetics of sufentanil administered by target-controlled infusion in Chinese patients.

机构信息

Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, China.

出版信息

Chin Med J (Engl). 2009 Sep 5;122(17):1979-84.

PMID:19781381

Abstract

BACKGROUND

Sufentanil is a suitable choice for target-controlled infusion (TCI) because of its shorter context-sensitive half-time. The current study was to estimate the pharmacokinetics of sufentanil TCI in Chinese patients using the two-stage analysis.

METHODS

Twelve adult patients with American Society of Anesthesiologists (ASA) physical status I or II undergoing elective surgery under general anesthesia were included. Anesthesia was induced with propofol, rocuronium and sufentanil administered by TCI lasting for 30 minutes, with target effect-site concentration of sufentanil 4 or 6 ng/ml. Frequent arterial blood samples (1.5 ml) were taken during and up to 24 hours after sufentanil TCI. Before the end of surgery, another arterial blood sample (1.0 ml) was drawn for the blood-gas analysis. Plasma sufentanil concentrations were determined by liquid chromatography-tandem mass spectrometry (limit of quantitation was 5 pg/ml). The data were analyzed with the two-stage approach, linear regression and correlation analysis.

RESULTS

The pharmacokinetics of sufentanil TCI were adequately described by a three-compartment model. The variables were derived as follows: the volume of central compartment (V(1)) was 5.4 L, volume of distribution at steady-state (Vdss) was 222.6 L, metabolic clearance (Cl(1)) was 0.84 L/min and elimination half-life (t(1/2Y)) was 389 minutes. Patients' age, gender and PaCO2 correlated significantly with the pharmacokinetic parameters. The Vdss, volume of slowly equilibrating compartment (V(3)) and t(1/2Y) increased, and rapid distribution clearance (Cl(2)) decreased with increasing patient age. Male patients had larger values of Vdss, volume of rapidly equilibrating compartment (V(2)) and V(3) than female patients. The Vdss and V(3) increased with higher PaCO2 values. There were no significant correlations between the pharmacokinetic variables and body weight, height, lean body mass, plasma albumin, sufentanil dose, duration of surgery, pH or base excess of blood (BE-B).

CONCLUSIONS

The pharmacokinetics of sufentanil TCI in Chinese patients can be optimally described by a three-compartment model. The pharmacokinetic analysis technique may affect the pharmacokinetic parameters and correlations.

摘要

背景

舒芬太尼因其较短的浓度时间敏感半衰期，是靶控输注（TCI）的理想选择。本研究旨在采用两阶段分析法，估算中国患者舒芬太尼 TCI 的药代动力学。

方法

选择 12 例 ASA 分级 I 或 II 级择期全麻手术患者，采用 TCI 输注舒芬太尼 30 分钟，目标效应室浓度为 4 或 6ng/ml。在 TCI 期间和结束后 24 小时内频繁采集动脉血样（1.5ml），在手术结束前再采集 1.0ml 动脉血样进行血气分析。采用液相色谱-串联质谱法（定量下限为 5pg/ml）测定血浆舒芬太尼浓度。采用两阶段法、线性回归和相关分析进行数据分析。

结果

舒芬太尼 TCI 的药代动力学可通过三室模型得到很好的描述。各变量值为：中央室容积（V1）为 5.4L，稳态分布容积（Vdss）为 222.6L，代谢清除率（Cl1）为 0.84L/min，消除半衰期（t1/2Y）为 389 分钟。患者年龄、性别和 PaCO2 与药代动力学参数显著相关。Vdss、缓慢平衡腔室容积（V3）和 t1/2Y 随患者年龄的增加而增加，快速分布清除率（Cl2）随年龄的增加而降低。男性患者的 Vdss、快速平衡腔室容积（V2）和 V3 值大于女性患者。Vdss 和 V3 随 PaCO2 值的升高而增加。药代动力学参数与体重、身高、瘦体重、血浆白蛋白、舒芬太尼剂量、手术时间、pH 值或血碱剩余（BE-B）之间无显著相关性。