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

• Published in: Clinical pharmacokinetics Vol. 49; no. 12; pp. 817 - 827
• Main Authors: Olesen, Anne E., Upton, Richard, Foster, David J. R., Staahl, Camilla, Christrup, Lona L., Arendt-Nielsen, Lars, Drewes, Asbjørn M.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.12.2010; Adis International; Wolters Kluwer Health, Inc; Springer Nature B.V
• Subjects: Acids; Administration, Oral; Adult; Analgesics, Opioid - pharmacokinetics; Analgesics, Opioid - pharmacology; Biological and medical sciences; Capsaicin; Complications and side effects; Cross-Over Studies; Dosage and administration; Double-Blind Method; Esophagus - pathology; Female; General pharmacology; Humans; Hyperalgesia - drug therapy; Internal Medicine; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Models, Biological; Original Research Article; Oxycodone; Oxycodone - pharmacokinetics; Oxycodone - pharmacology; Pain Measurement; Pharmacokinetics; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pharmacotherapy; Time Factors; Young Adult; Denmark; Pain Measure; Capsaicin; Opioid Receptor; Oxycodone; Oxymorphone; Human; Pharmacokinetic pharmacodynamic relationship; Nervous system diseases; Pain; Oral administration; Opiates; Models; Narcotic analgesic; Hyperalgesia
• DOI: 10.2165/11536610-000000000-00000
• ISSN: 0312-5963; 1179-1926

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 (E max ) 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.