The effect of the base on the kinetics of action of the capsaicinoid nonivamide: Evaluation with a hyperemic test

Because of their selective receptor-mediated action on cutaneous nociceptiv e C-fibers, the interest in capsaicinoids as topical analgetic drugs has be en constantly growing over the past yea rs. Knowledge of the pharmacokineti cs seems particularly important for potential future clinical applications. Therefore, the aim of the present study was to investigate the influence o f the type of preparation on the time course of action of the capsaicinoid nonivamide monitored by the axon-reflex-induced hyperemic action and area o f erythema. Sixteen healthy subjects were included in the study. The hypere mic responses after application of nonivamide in an oil-in-water (O/W) emul sion and in a water-free ointment were assessed both by laser Doppler perfu sion 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 ni coboxil and a combination of nonivamide and nicoboxil in the same preparati ons. Applied as a water-free ointment, nonivamide showed a slow onset of hy peremic 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 re vealed a clearly lesser influence of the base regarding the onset of maximu m 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 t he water-free ointment and the O/W emulsion base. In conclusion, the result s 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 hypere mic test used in this paper is very useful for the quantitative determinati on of the pharmacokinetic properties of capsaicinoids. Moreover, the C-fibe r-stimulating effect of capsaicinoids can, at least in part, be enhanced by combination with a nicotinic ester, even though these substances have no d irect effect on the C-fibers.