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Type: Journal article
Title: Pharmacokinetic-pharmacodynamic modeling of morphine and oxycodone concentrations and analgesic effect in a multimodal experimental pain model
Author: Staahl, C.
Upton, R.
Foster, D.
Christrup, L.
Kristensen, K.
Hansen, S.
Arendt-Nielsen, L.
Drewes, A.
Citation: Journal of Clinical Pharmacology, 2008; 48(5):619-631
Publisher: Sage Publications Inc
Issue Date: 2008
ISSN: 0091-2700
Statement of
Camilla Staahl, Richard Upton, David J. R. Foster, Lona Louring Christrup, Kim Kristensen, Steen Honoré Hansen, Lars Arendt-Nielsen and Asbjørn Mohr Drewes
Abstract: Analgesia from most opioids is mediated by µ 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.
Keywords: experimental pain; pharmacodynamics, pharmaco kinetics; oxycodone; morphine
Description: Copyright © 2008 by the American College of Clinical Pharmacology
RMID: 0020080548
DOI: 10.1177/0091270008314465
Appears in Collections:Medicine publications

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