给药方法和协变量对成年志愿者丙泊酚药代动力学的影响。

The influence of method of administration and covariates on the pharmacokinetics of propofol in adult volunteers.

作者信息

Schnider T W, Minto C F, Gambus P L, Andresen C, Goodale D B, Shafer S L, Youngs E J

机构信息

Institut für Anästhesie und Intensivmedizin, Inselspital, Universität Bern, Switzerland.

出版信息

Anesthesiology. 1998 May;88(5):1170-82. doi: 10.1097/00000542-199805000-00006.

DOI:10.1097/00000542-199805000-00006

PMID:9605675

Abstract

BACKGROUND

Unresolved issues with propofol include whether the pharmacokinetics are linear with dose, are influenced by method of administration (bolus vs. infusion), or are influenced by age. Recently, a new formulation of propofol emulsion, containing disodium edetate (EDTA), was introduced in the United States. Addition of EDTA was found by the manufacturer to significantly reduce bacterial growth. This study investigated the influences of method of administration, infusion rate, patient covariates, and EDTA on the pharmacokinetics of propofol.

METHODS

Twenty-four healthy volunteers aged 26-81 yr were given a bolus dose of propofol, followed 1 h later by a 60-min infusion. Each volunteer was randomly assigned to an infusion rate of 25, 50, 100, or 200 microg x kg(-1) x min(-1). Each volunteer was studied twice under otherwise identical circumstances: once receiving propofol without EDTA and once receiving propofol with EDTA. The influence of the method of administration and of the volunteer covariates was explored by fitting a three-compartment mamillary model to the data. The influence of EDTA was investigated by direct comparison of the measured concentrations in both sessions.

RESULTS

The concentrations of propofol with and without EDTA were not significantly different. The concentration measurements after the bolus dose were significantly underpredicted by the parameters obtained just from the infusion data. The kinetics of propofol were linear within the infusion range of 25-200 microg x kg(-1) x min(-1). Age was a significant covariate for Volume2 and Clearance2, as were weight, height, and lean body mass for the metabolic clearance.

CONCLUSIONS

These results demonstrate that method of administration (bolus vs. infusion), but not EDTA, influences the pharmacokinetics of propofol. Within the clinically relevant range, the kinetics of propofol during infusions are linear regarding infusion rate.

摘要

背景

丙泊酚存在一些尚未解决的问题，包括其药代动力学是否与剂量呈线性关系、是否受给药方式（推注与输注）影响或是否受年龄影响。最近，一种含有乙二胺四乙酸二钠（EDTA）的新型丙泊酚乳剂在美国上市。制造商发现添加EDTA可显著减少细菌生长。本研究调查了给药方式、输注速率、患者协变量和EDTA对丙泊酚药代动力学的影响。

方法

24名年龄在26 - 81岁的健康志愿者先接受一次丙泊酚推注剂量，1小时后再进行60分钟的输注。每名志愿者被随机分配到25、50、100或200微克·千克⁻¹·分钟⁻¹的输注速率组。每名志愿者在其他条件相同的情况下接受两次研究：一次接受不含EDTA的丙泊酚，一次接受含EDTA的丙泊酚。通过将三室乳突模型拟合到数据中来探讨给药方式和志愿者协变量的影响。通过直接比较两次研究中测得的浓度来研究EDTA的影响。