Clinical Pharmacokinetics

, Volume 49, Issue 12, pp 817–827 | Cite as

A Pharmacokinetic and Pharmacodynamic Study of Oral Oxycodone in a Human Experimental Pain Model of Hyperalgesia

  • Anne E. Olesen
  • Richard Upton
  • David J. R. Foster
  • Camilla Staahl
  • Lona L. Christrup
  • Lars Arendt-Nielsen
  • Asbjørn M. DrewesEmail author
Original Research Article


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.


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.


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).


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.


Capsaicin Opioid Receptor Oxycodone Pain Measure Oxymorphone 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The study was supported by Norpharma (Mundipharma), “Det Obelske Familie Fond”, the Spar Nord Foundation, Hertha Christensens Fond and Institute of Clinical Medicine, Aarhus University. The authors declare that there are no conflicts of interest related to the study.

Supplementary material

40262_2012_49120817_MOESM1_ESM.pdf (919 kb)
Supplementary material, approximately 941 KB.


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Copyright information

© Adis Data Information BV 2010

Authors and Affiliations

  • Anne E. Olesen
    • 1
    • 2
  • Richard Upton
    • 3
  • David J. R. Foster
    • 4
  • Camilla Staahl
    • 1
    • 2
  • Lona L. Christrup
    • 5
  • Lars Arendt-Nielsen
    • 2
  • Asbjørn M. Drewes
    • 1
    • 2
    Email author
  1. 1.Mech-Sense, Department of Gastroenterology, Aalborg HospitalAarhus University HospitalAalborgDenmark
  2. 2.Center for Sensory-Motor Interactions (SMI), Department of Health Science and TechnologyAalborg UniversityAalborgDenmark
  3. 3.Department of Anesthesia and Intensive Care, Royal Adelaide HospitalUniversity of AdelaideAdelaideAustralia
  4. 4.School of Pharmacy and Medical Sciences and Sansom InstituteUniversity of South AustraliaAdelaideAustralia
  5. 5.Department of Pharmacology and Pharmacotherapy, Faculty of Pharmaceutical SciencesUniversity of CopenhagenCopenhagenDenmark

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