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.
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 10mg/morphine 20mg, 3.00 and 1.63 respectively for oxycodone 15 mg/morphine 30 mg, and 1.12 and 1.25 respectively for oxycodone 20mg/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, 20mg) was considered to be clinically relevant based on a difference from placebo of ≥ 2.5 μV. 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/antihyperalgesic effects of 2 opioids.
Janssen Research and Development, Janssen Pharmaceutica N.V., Beerse, Belgium HPR - Human Pharmacodynamic Research GmbH, Munich, Germany.
Eef
E
Hoeben
Johan W
JW
Smit
David
D
Upmalis
Sarah
S
Rusch
Klaus
K
Schaffler
Peter
P
Reitmeir
Bernhard
B
Mangold
D000284:Administration, Oral; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage; D002211:Capsaicin; D004305:Dose-Response Relationship, Drug; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects*; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D007834:Lasers; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage*; D010098:Oxycodone / Q000008:administration & dosage*; D012867:Skin / Q000187:drug effects / Q000503:physiopathology / Q000528:radiation effects; D016896:Treatment Outcome; D014466:Ultraviolet Rays
D000701:Analgesics, Opioid; D009020:Morphine; D010098:Oxycodone; D002211:Capsaicin