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.

Evaluation of changes in the haemoglobin of skin and muscle tissue of the calf, as induced by topical application of a nonivamide/nicoboxil cream

“…Stücker et al (1999) described the effects on cutaneous blood circulation in detail for nonivamide, nicoboxil, and a combination of both compounds. In addition to these previous findings, our investigation demonstrates that administration of N/N cream augments cutaneous concentration of oxyHb and elevates SO 2 .…”

Evaluation of haemoglobin changes of skin and muscle tissue of the calf induced by topical application of a nonivamide / nicoboxil cream

“…Stücker et al [31] described the effects on cutaneous blood circulation in detail for nonivamide, nicoboxil and the combination of both compounds. In addition to these previous findings, our investigation demonstrates that administration of the nonivamide / nicoboxil combination augments cutaneous concentration of oxyHb and elevates SO2.…”

Comparison of capillary and venous blood in the analysis of concentration and function of leucocyte sub-populations

“…1) may also suggest that the routinely used methods adopted in this research to increase blood flow to these sampling sites, either via action of nonivamide and butoxyethyl nicotinate containing cream-Finalgon ® (Zavorsky et al 2005;Schommer et al 2012;Beneke and Alkhatib 2015) or submersion of limb in hot water, may have contributed to neutrophil activation. Nonivamide has been described to, when applied to the skin, induce release of vasodilative polypeptides such as calcitonin-gene-related peptide (CGRP) and substance P (Stucker et al 1999). CGRP has been shown to promote accumulation of inflammatory cells in areas of inflammation and to enhance neutrophilic adhesion to the endothelium in vitro (Hartung and Toyka 1989;Zimmerman et al 1992).…”