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 cm2. 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.