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

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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.

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Acknowledgements

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.

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Authors and Affiliations

  1. Mech-Sense, Department of Gastroenterology, Aalborg Hospital, Aarhus University Hospital, Hobrovej 18-22, 9000, Aalborg, Denmark

    Anne E. Olesen, Camilla Staahl &  Asbjørn M. Drewes

  2. Center for Sensory-Motor Interactions (SMI), Department of Health Science and Technology, Aalborg University, Aalborg, Denmark

    Anne E. Olesen, Camilla Staahl, Lars Arendt-Nielsen &  Asbjørn M. Drewes

  3. Department of Anesthesia and Intensive Care, Royal Adelaide Hospital, University of Adelaide, Adelaide, South Australia, Australia

    Richard Upton

  4. School of Pharmacy and Medical Sciences and Sansom Institute, University of South Australia, Adelaide, South Australia, Australia

    David J. R. Foster

  5. Department of Pharmacology and Pharmacotherapy, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark

    Lona L. Christrup

Authors
  1. Anne E. Olesen
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  2. Richard Upton
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  3. David J. R. Foster
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  4. Camilla Staahl
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  5. Lona L. Christrup
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  6. Lars Arendt-Nielsen
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  7. Asbjørn M. Drewes
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Correspondence to Asbjørn M. Drewes.

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Olesen, A.E., Upton, R., Foster, D.J.R. et al. A Pharmacokinetic and Pharmacodynamic Study of Oral Oxycodone in a Human Experimental Pain Model of Hyperalgesia. Clin Pharmacokinet 49, 817–827 (2010). https://doi.org/10.2165/11536610-000000000-00000

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