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https://hdl.handle.net/2440/62735
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Type: | Journal article |
Title: | A pharmacokinetic and pharmacodynamic study of oral oxycodone in a human experimental pain model of hyperalgesia |
Author: | Olesen, A. Upton, R. Foster, D. Staahl, C. Christrup, L. Arendt-Nielsen, L. Drewes, A. |
Citation: | Clinical Pharmacokinetics, 2010; 49(12):817-827 |
Publisher: | Adis International Ltd |
Issue Date: | 2010 |
ISSN: | 0312-5963 1179-1926 |
Statement of Responsibility: | Anne E. Olesen, Richard Upton, David J.R. Foster, Camilla Staahl, Lona L. Christrup, Lars Arendt-Nielsen and Asbjørn M. Drewes |
Abstract: | Background and Objective: Oxycodone is not as well characterized, with respect to its pharmacokinetic/pharmacodynamic properties, as other opioids. Moreover, the pharmacodynamic profile of oxycodone can be affected by changes in the pain system, e.g. hyperalgesia. Therefore, the aim of this study was to investigate the pharmacokinetic/pharmacodynamic profiles of oxycodone in a human experimental pain model of hyperalgesia. Methods: Twenty-four healthy subjects received oral oxycodone (15 mg) or placebo. Pharmacodynamics were assessed utilizing a multimodal, multi-tissue paradigm where pain was assessed from skin (heat), muscle (pressure) and viscera (heat and electricity) before and 30, 60 and 90 minutes after induction of generalized hyperalgesia evoked by perfusion of acid and capsaicin in the oesophagus. Venous blood samples were obtained for quantification of oxycodone plasma concentrations before and 5, 10, 15, 30, 45, 60, 90 and 120 minutes after drug administration. Results: Oxycodone blood concentrations could be described by a one-compartment model but, given the necessarily short timescale of the study, the concentrations were represented by linear interpolation for subsequent pharmacodynamic models. Time-dependent changes in the pain measures in the placebo arm of the study were represented by linear or quadratic functions. The time course of the pain measures in the oxycodone arm was taken to be the time course for the placebo arm plus a concentration-effect relationship that was either zero (no drug effect), linear or a maximum effect (Emax) model. For three of the four pain measures, there was a time-dependent change after administration of placebo (e.g. due to the development of generalized hyperalgesia). Conclusion: There was a measurable effect of oxycodone, compared with placebo, on all pain measures, and a linear concentration-effect relationship without an effect delay was demonstrated. This could indicate an initial peripheral analgesic effect of oxycodone. |
Keywords: | Esophagus Humans Hyperalgesia Acids Oxycodone Capsaicin Analgesics, Opioid Pain Measurement Administration, Oral Cross-Over Studies Double-Blind Method Models, Biological Time Factors Adult Middle Aged Female Male Young Adult |
Rights: | © 2010 Adis Data Information BV. All rights reserved. |
DOI: | 10.2165/11536610-000000000-00000 |
Published version: | http://dx.doi.org/10.2165/11536610-000000000-00000 |
Appears in Collections: | Anaesthesia and Intensive Care publications Aurora harvest |
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