Pharmacodynamic measurements of methyl nicotinate percutaneous absorption: the effect of aging on microcirculation

Abstract

The penetration of drugs through aged skin is important both in terms of transdermal delivery to elicit systemic pharmacological effects, and for topical treatment. Cutaneous microcirculation efficiency, an integral parameter in the overall process of percutaneous absorption, was studied in young (20-34 years) and old (64-86 years) individuals. Cutaneous erythema as induced by topical administration of methyl nicotinate to the ventral forearm, was monitored non-invasively using laser-Doppler flowmetry. Dose-response behaviour was characterized by five parameters: (i) the time of onset of action; (ii) the time to reach maximum response; (iii) the magnitude of the maximum response; (iv) the area under the response-time curve; and (v) the time to decay to 75% of the maximum response. Additionally, the sensitivity and efficiency of the cutaneous microcirculation in both age groups was evaluated using a pharmacokinetic-pharmacodynamic model. Statistical analysis of all data showed no significant differences between the age groups for the same concentrations. The results indicate that microvessel reactivity to the applied stimulus is comparable in the ventral forearm of both young and old populations.

Exploring human in vivo microcirculation with methyl nicotinate in different perfusion conditions

“…Estes testes alteram as condições de perfusão, quer sistemicamente, como em alterações posturais [5] , na oclusão de um membro [5] e na inalação de oxigénio [6] quer localmente, como na estimulação térmica [7] , e na aplicação de fármacos [8] . O nicotinato de metilo (NM) é um potente vasodilatador que tem sido utilizado para avaliar a reactividade microvascular cutânea [8][9][10][11][12] . A aplicação tópica de NM induz uma rápida vasodilatação local, expressa através de um eritema cutâneo, facilmente registado com FLD [8,9] .…”

“…A aplicação tópica de NM induz uma rápida vasodilatação local, expressa através de um eritema cutâneo, facilmente registado com FLD [8,9] . Os efeitos da idade [9] , do género [12] e da zona da pele [10,13] na resposta ao NM foram já estudados. No entanto, o efeito das condições de perfusão locais nesta resposta necessita de esclarecimento.…”

“…O nicotinato de metilo (NM) é um potente vasodilatador que tem sido utilizado para avaliar a reactividade microvascular cutânea [8][9][10][11][12] . A aplicação tópica de NM induz uma rápida vasodilatação local, expressa através de um eritema cutâneo, facilmente registado com FLD [8,9] . Os efeitos da idade [9] , do género [12] e da zona da pele [10,13] na resposta ao NM foram já estudados.…”

“…Topical application of MN induces a rapid local vasodilatation, clinically expressed as a cutaneous erythema, easily recorded with LDF [8,9] . The effects of age [9] , gender [12] and skin location [10,13] on the response to MN have already been studied and described. However, the effect of local perfusion conditions in this response needs clarification.…”

“…These tests modify perfusion conditions, either systemically, as with postural changes [5] , limb occlusion, [5] and oxygen breathing, [6] or locally, as with thermal stimulation [7] and topical drug application [8] . Methyl nicotinate (MN) is a potent vasodilator that has been previously used to assess skin microvascular reactivity [8][9][10][11][12] . Topical application of MN induces a rapid local vasodilatation, clinically expressed as a cutaneous erythema, easily recorded with LDF [8,9] .…”