Time of erythema onset after application of methyl nicotinate ointments as response parameter: influence of penetration kinetics and enhancing agents.
The time of erythema onset may be used as a response parameter for quantification of the cutaneous erythema response induced by methyl nicotinate. The vehicles light mineral oil (LMO; test) and medium chain triglycerides (MCT; standard) were compared with regard to the pharmacodynamic response. Moreover, the influence of penetration enhancers on the time of erythema onset was investigated under zero order penetration kinetics. The enhancers dimethyl sulfoxide, diethylene glycol monoethyl ether and three different glycerides in different concentrations were added to MCT as a standard vehicle. All preparations were applied to the forearms of volunteers under infinite dose conditions at different thermodynamic drug activity levels (0.2-3.2% of the saturation level) and different drug concentrations (0.051-0.816%), respectively. Different penetration kinetics do not influence data of erythema onset, as these data are comparable to those obtained under finite dose conditions (first order penetration kinetics). With regard to the penetration enhancers, a significantly enhanced penetration of methyl nicotinate could be observed only for diethylene glycol monoethyl ether and dimethyl sulfoxide. However, no significant difference between light mineral oil and MCT could be found with regard to penetration enhancement. The time of erythema onset is an easy and efficient parameter for quantification of the pharmacodynamic response caused by nicotinates.
Remane
Y
Y
Institute for Pharmacy, Department of Pharmaceutical Technology, University of Hamburg, Hamburg, Germany.
Leopold
C S
CS
D000328:Adult; D000465:Algorithms; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D004890:Erythema / Q000139:chemically induced*; D005260:Female; D006801:Humans; D008051:Lipid Bilayers; D008297:Male; D008875:Middle Aged; D009539:Nicotinic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D009824:Ointments; D012869:Skin Absorption / Q000502:physiology; D013816:Thermodynamics
D008051:Lipid Bilayers; D009539:Nicotinic Acids; D009824:Ointments; C008473:methyl nicotinate