Dose-response relationship after single oral dose administrations of morphine and oxycodone using laser-evoked potentials on UVB- and capsaicin-irritated skin in healthy male subjects

Eef Hoeben, Johan W. Smit, David Upmalis, Sarah Rusch, Klaus Schaffler, Peter Reitmeir, Bernhard Mangold    http://dx.doi.org/10.1016/j.pain.2012.04.018

in PAIN 153 (2012) 1648–1656 (full paper here:)

Abstract: The aim of the study was to evaluate the analgesic/antihyperalgesic efficacy and to establish the dose-response relationship of morphine immediate release (IR) and oxycodone IR in a human experimental algesimetric model. Calculated effect ratios for peak-to-peak (PtP) amplitudes of laser-evoked potentials (LEPs) and visual analog scales (VAS) postlaser pain on UVB-irradiated skin (main target variables) were 1.68 and 1.18 respectively for oxycodone 10 mg/morphine 20 mg, 3.00 and 1.63 respectively for oxycodone 15 mg/morphine 30 mg, and 1.12 and 1.25 respectively for oxycodone 20 mg/morphine 40 mg. The effect on the laser-PtP amplitude of morphine at the highest dose (40 mg) and of oxycodone at all doses (10, 15, 20 mg) was considered to be clinically relevant based on a difference from placebo of >2.5 micV.
For both compounds, a statistically significant linear trend was observed between dose groups in at least 1 of the 2 main target variables (adjusted P value for both end points <.001 at all doses). Hyperalgesia developed over time vs baseline due to acute exposure to UVB irradiation and to topical/occlusive 1% capsaicin solution. For both compounds, the principal onset of analgesic/antihyperalgesic drug effects was around 0.5 hours with an average peak at about 1 to 2 hours and the effect lasting for more than 3 hours (morphine 20 and 30 mg) or 6 hours (morphine 40 mg and oxycodone all doses).
In conclusion, the study demonstrated a solid outcome of a mixed objective/subjective human experimental algesimetric model to approach dose-response relationships and analgesic/anti-hyperalgesic effects of 2 opioids.

About Klaus Schaffler

Dr. med. Klaus Schaffler (MD) has been specializing in the electrophysiology and pharmacology of the human central nervous system (CNS) – as well as in the field of human experimental pain research. During this development process, HPR Dr. Schaffler GmbH has issued over 175 presentations/ publications (sharing more than 50 on pain/ analgesia) and has conducted more than 150 phase-I studies with quite different objectives.
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