HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:
Sign In to gain access to subscriptions and/or personal tools.

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Request Reprints Google Scholar Articles by Staahl, C. Articles by Drewes, A. M. PubMed PubMed Citation Articles by Staahl, C. Articles by Drewes, A. M.

Pharmacokinetic-Pharmacodynamic Modeling of Morphine and Oxycodone Concentrations and Analgesic Effect in a Multimodal Experimental Pain Model

From the Department of Gastroenterology, Center for Visceral Biomechanics and Pain, University Hospital Aalborg, Denmark (Dr Staahl, Dr Drewes); the Department of Health Science and Technology, Center for Sensory-Motor Interactions (SMI), Aalborg University, Denmark (Dr Staahl, Dr Arendt-Nielsen, Dr Drewes); Discipline of Anaesthesia and Intensive Care, Royal Adelaide Hospital, The University of Adelaide, Adelaide, Australia (Dr Upton); School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia (Dr Foster); Department of Pharmacology and Pharmacotherapy, Copenhagen University, Copenhagen, Denmark (Dr Christrup); Department of Clinical Pharmacology, Astrazeneca, Lund, Sweden (Dr Kristensen); and Department of Pharmacy and Analytical Chemistry, Copenhagen University, Copenhagen, Denmark (Dr Hansen).

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.

Key Words: Experimental pain • pharmacodynamics, pharmaco kinetics • oxycodone • morphine

Address for correspondence: Camilla Staahl, Center for Visceral Biomechanics and Pain, Department of Gastroenterology, University Hospital Aalborg, Hobrovej 18-22, 9000 Aalborg, Denmark; e-mail: cst{at}smi.auc.dk.