The influence of method of administration and covariates on the pharmacokinetics of propofol in adult volunteers
The influence of method of administration and covariates on the pharmacokinetics of propofol in adult volunteers
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DOI：
10.1097/00000542-199805000-00006
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发表时间：
1998-05-01
期刊：
影响因子：
8.8
通讯作者：
Youngs, EJ
中科院分区：
文献类型：
--
作者：
Schnider, TW;Minto, CF;Youngs, EJ
背景资料：丙泊酚未解决的问题包括药代动力学是否与剂量呈线性关系，是否受给药方法（推注vs.输注）影响，或是否受年龄影响。最近，美国引进了一种含有乙二胺四乙酸二钠（EDTA）的丙泊酚乳剂新制剂。生产商发现添加EDTA可显著减少细菌生长。本研究探讨了管理方法，输注速率，患者的协变量，和EDTA的影响，对propofulfon.Methods：24名健康志愿者年龄在26-81岁的药代动力学给予丙泊酚的推注剂量，随后1小时后，由60分钟输注。每名志愿者被随机分配到25、50、100或200 mu的输注速率g.kg（-1）.min（-1）。在其他相同的情况下对每名志愿者进行研究：一次接受不含EDTA的丙泊酚，一次接受含EDTA的丙泊酚。通过将三室乳头模型拟合至数据，探索给药方法和志愿者协变量的影响。结果：EDTA组与对照组异丙酚血药浓度无显著性差异。仅从输注数据获得的参数显著低估了推注给药后的浓度测量值。异丙酚的输注动力学在25-200 μ g·min ~（-1）范围内呈线性。g.kg年龄是一个显着的协变量的体积（2）和清除率（2），是体重，身高和瘦体重的代谢clearance.Conclusions：这些结果表明，给药方法（推注与输液），但不是EDTA，影响丙泊酚的药代动力学。在临床相关范围内，输注期间丙泊酚的动力学与输注速率呈线性关系。
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 mu g.kg(-1).min(-1). Each volunteer was studied tn ice 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 mere 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 mu g.kg(-1).min(-1). Age was a significant covariate for Volume(2) and Clearance(2), 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.