Methodology to measure the transient effect of occlusion on skin penetration and stratum corneum hydration in vivo.
The effect of short duration occlusion on skin penetration and stratum corneum water content was studied in vivo in eight human subjects. Percutaneous absorption of hexyl nicotinate was monitored non-invasively by laser Doppler velocimetry (LDV) following each of three randomly assigned pre-treatments: untreated control, 30 min occlusion with a polypropylene chamber and 30 min occlusion followed by exposure to ambient conditions for 1 h. Stratum corneum water content after the same pre-treatments was measured with the dielectric probe technique. The local vasodilatory effect of the nicotinic acid ester was quantified using LDV by the onset of increased blood flow, the time of maximal increase in response, the magnitude of the peak response and the area under the response-time curve. Each of these parameters was significantly different, immediately following occlusion, from the untreated control values. However, if the occluded site was exposed for 1 h prior to hexyl nicotinate application these parameters did not differ significantly from the controls. Stratum corneum water content (expressed as a percentage of a maximal value) showed the same behaviour: the pre-treatment control value was 31.8 +/- 4.8%; after 30 min occlusion, this had risen to 46.9 +/- 6.2%; 1 h later, the reading had returned to 32.1 +/- 6.2%. There was a significant correlation between stratum corneum water content and area under the LDV response-time curve. It appears, therefore, that this method may be useful for quantifying the relationship between increased stratum corneum hydration and enhanced percutaneous absorption in vivo in man.
Ryatt
K S
KS
Department of Pharmacy, School of Pharmacy, University of California, San Francisco 94143.
Mobayen
M
M
Stevenson
J M
JM
Maibach
H I
HI
Guy
R H
RH
D000328:Adult; D006801:Humans; D008297:Male; D009539:Nicotinic Acids / Q000493:pharmacokinetics*; D009779:Occlusive Dressings; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D012869:Skin Absorption; D014867:Water / Q000378:metabolism*
D009539:Nicotinic Acids; D014867:Water; C049457:hexyl nicotinate