title: Validation of the simplified UVB model to assess the pharmacodynamics of analgesics in healthy human volunteers.
abstract: A pharmacokinetic/pharmacodynamic, randomized, crossover, placebo-controlled study was conducted in healthy human volunteers with the primary objective of exploring the existence of a positive interaction between paracetamol 1 g and ketorolac 20 mg intravenously on experimental pain  models. Further, the simplified UVB model was validated as a screening tool for analgesics or a combination of analgesics in clinical drug development. It was observed that the UVB irradiation induced primary hyperalgesia, evidenced by significant decreases of the heat pain threshold from  (mean ± SD) 46.9 ± 1.1 °C to 40.1 ± 1.7 °C (p <0.001) and of the mechanical pain threshold (62% decrease). A small intra- and inter-individual variability was observed as well as consistent intra-day stability for the heat pain threshold. The UVB irradiation  also resulted in the development of an area of secondary hyperalgesia of 21.3 ± 11.3 cm(2). The mechanical pain threshold and area of secondary hyperalgesia showed small intra-individual variability and consistent intra-day stability. However, a greater variability was observed  between subjects, which suggests that a crossover design would allow limiting the number of subjects.
authors.affiliation: Division of clinical pharmacology and toxicology University Hospitals of Geneva Rue Gabrielle-Perret-Gentil 4, CH-1211 Geneva, Switzerland.
authors.forename: Kuntheavy
authors.initials: K
authors.lastname: Ing Lorenzini
authors.forename: Marie
authors.initials: M
authors.lastname: Besson
authors.forename: Youssef
authors.initials: Y
authors.lastname: Daali
authors.forename: Denis
authors.initials: D
authors.lastname: Salomon
authors.forename: Pierre
authors.initials: P
authors.lastname: Dayer
authors.forename: Jules
authors.initials: J
authors.lastname: Desmeules
mesh_terms: D000082:Acetaminophen / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000328:Adult; D000700:Analgesics / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018712:Analgesics, Non-Narcotic / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004338:Drug Combinations; D005240:Feasibility Studies; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy; D007275:Injections, Intravenous; D020910:Ketorolac / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D013471:Sunburn / Q000188:drug therapy* / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D000700:Analgesics; D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004338:Drug Combinations; D000082:Acetaminophen; D020910:Ketorolac