多模式实验性疼痛模型中吗啡和羟考酮浓度与镇痛效果的药代动力学-药效学建模

Pharmacokinetic-pharmacodynamic modeling of morphine and oxycodone concentrations and analgesic effect in a multimodal experimental pain model.

作者信息

Staahl Camilla, Upton Richard, Foster David J R, Christrup Lona Louring, Kristensen Kim, Hansen Steen Honoré, Arendt-Nielsen Lars, Drewes Asbjørn Mohr

机构信息

Center for Visceral Biomechanics and Pain, Department of Gastroenterology, University Hospital Aalborg, Hobrovej 18-22, 9000 Aalborg, Denmark.

出版信息

J Clin Pharmacol. 2008 May;48(5):619-31. doi: 10.1177/0091270008314465.

Abstract

Analgesia from most opioids is mediated by mu receptors located mainly in the central nervous system. Previous studies have shown a different pharmacological profile of oxycodone in respect to visceral analgesia. This study investigated if morphine and oxycodone have different pharmacokinetic/pharmacodynamic profiles, in particular with respect to delay between opioid blood concentration and analgesia. Twenty-four healthy subjects had oral morphine (30 mg), oxycodone (15 mg), or placebo. Mechanical, thermal, and electrical pain tests were performed in the skin and viscera. Blood samples and pain measurements were taken at baseline and after 15, 30, 60, 90, and 120 minutes. Pharmacokinetic/pharmacodynamic profiles were modeled using a 2-stage, nonlinear, mixed-effects approach with an effect compartment to represent the concentration-analgesia delay. Morphine kinetics was best described by a 2-compartment model, whereas oxycodone kinetics was best described with a 1-compartment model. Generally the analgesic effects of morphine were best related to plasma concentration by introducing a delay via an effect compartment. However, for oxycodone, this was only the case for analgesia in the somatic pain measures, whereas the plasma concentration correlated better to the course of the analgesia with no delay in the visceral pain measures. Oxycodone and morphine showed different pharmacodynamic/pharmacokinetic relationships for the visceral analgesia, whereas relationships were alike for somatic analgesia.

摘要

大多数阿片类药物的镇痛作用是由主要位于中枢神经系统的μ受体介导的。先前的研究表明,羟考酮在内脏镇痛方面具有不同的药理学特征。本研究调查了吗啡和羟考酮是否具有不同的药代动力学/药效学特征,特别是在阿片类药物血药浓度与镇痛之间的延迟方面。24名健康受试者口服吗啡(30毫克)、羟考酮(15毫克)或安慰剂。在皮肤和内脏进行机械、热和电疼痛测试。在基线以及15、30、60、90和120分钟后采集血样并进行疼痛测量。使用两阶段非线性混合效应方法对药代动力学/药效学特征进行建模,采用效应室来表示浓度-镇痛延迟。吗啡动力学最好用二室模型描述,而羟考酮动力学最好用一室模型描述。一般来说,通过效应室引入延迟后,吗啡的镇痛效果与血浆浓度的相关性最佳。然而,对于羟考酮,仅在躯体疼痛测量的镇痛方面是这种情况,而在没有延迟的内脏疼痛测量中,血浆浓度与镇痛过程的相关性更好。羟考酮和吗啡在内脏镇痛方面表现出不同的药效学/药代动力学关系,而在躯体镇痛方面关系相似。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索