Validation of the simplified UVB model to assess the pharmacodynamics of analgesics in healthy human volunteers

Chimia (Aarau). 2012;66(5):296-9. doi: 10.2533/chimia.2012.296.

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.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen / pharmacokinetics
  • Acetaminophen / therapeutic use*
  • Adult
  • Analgesics / pharmacokinetics
  • Analgesics / therapeutic use*
  • Analgesics, Non-Narcotic / pharmacokinetics
  • Analgesics, Non-Narcotic / therapeutic use*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Cross-Over Studies
  • Double-Blind Method
  • Drug Combinations
  • Feasibility Studies
  • Humans
  • Hyperalgesia / drug therapy
  • Injections, Intravenous
  • Ketorolac / pharmacokinetics
  • Ketorolac / therapeutic use*
  • Male
  • Middle Aged
  • Models, Biological
  • Pain Measurement
  • Pain Threshold / drug effects
  • Sunburn / drug therapy*
  • Sunburn / metabolism
  • Ultraviolet Rays / adverse effects*
  • Young Adult

Substances

  • Analgesics
  • Analgesics, Non-Narcotic
  • Anti-Inflammatory Agents, Non-Steroidal
  • Drug Combinations
  • Acetaminophen
  • Ketorolac