The Effect of the Base on the Kinetics of Action of the Capsaicinoid Nonivamide: Evaluation with a Hyperemic Test

Abstract

Because of their selective receptor-mediated action on cutaneous nociceptive C-fibers, the interest in capsaicinoids as topical analgetic drugs has been constantly growing over the past years. Knowledge of the pharmacokinetics seems particularly important for potential future clinical applications. Therefore, the aim of the present study was to investigate the influence of the type of preparation on the time course of action of the capsaicinoid nonivamide monitored by the axon-reflex-induced hyperemic action and area of erythema. Sixteen healthy subjects were included in the study. The hyperemic responses after application of nonivamide in an oil-in-water (O/W) emulsion and in a water-free ointment were assessed both by laser Doppler perfusion imaging and planimetry after 0, 15, 30, 45, 60, 120 and 240 min. They were compared with the reaction after application of the nicotinic ester nicoboxil and a combination of nonivamide and nicoboxil in the same preparations. Applied as a water-free ointment, nonivamide showed a slow onset of hyperemic action, reaching its maximum 45 min after application. When applied as an O/W emulsion, however, the increase in effect was high, reaching its maximum already after 30 min. Application of the nicoboxil preparations revealed a clearly lesser influence of the base regarding the onset of maximum effect. The combination of both substances showed an additive effect for both bases, and a maximum effect was found already after 15 min with both the water-free ointment and the O/W emulsion base. In conclusion, the results of the present study show that there appears to be a strong influence of the vehicle on the kinetics of action of capsaicinoids, and that the hyperemic test used in this paper is very useful for the quantitative determination of the pharmacokinetic properties of capsaicinoids. Moreover, the C-fiber-stimulating effect of capsaicinoids can, at least in part, be enhanced by combination with a nicotinic ester, even though these substances have no direct effect on the C-fibers.