Pharmacodynamic measurements of methyl nicotinate percutaneous absorption: the effect of aging on microcirculation.
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.
Roskos
K V
KV
Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco 94143.
Bircher
A J
AJ
Maibach
H I
HI
Guy
R H
RH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004305:Dose-Response Relationship, Drug; D005069:Evaluation Studies as Topic; D005260:Female; D006801:Humans; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D008875:Middle Aged; D009539:Nicotinic Acids / Q000493:pharmacokinetics / Q000494:pharmacology*; D012867:Skin / Q000098:blood supply*; D012869:Skin Absorption / Q000187:drug effects*; D015595:Skin Aging / Q000502:physiology*
D009539:Nicotinic Acids; C008473:methyl nicotinate