The kinetics of transdermal ethanol exchange.
The kinetics of ethanol transport from the blood to the skin surface are incompletely understood. We present a mathematical model to predict the transient exchange of ethanol across the skin while it is being absorbed from the gut and eliminated from the body. The model simulates the behavior of a commercial device that is used to estimate the blood alcohol concentration (BAC). During the elimination phase, the stratum corneum of the skin has a higher ethanol concentration than the blood. We studied the effect of varying the maximum BAC and the absorption rate from the gut on the relationship between BAC and equivalent concentration in the gas phase above the skin. The results showed that the ethanol concentration in the gas compartment always took longer to reach its maximum, had a lower maximum, and had a slower apparent elimination rate than the BAC. These effects increased as the maximum BAC increased. Our model's predictions are consistent with experimental data from the literature. We performed a sensitivity analysis (using Latin hypercube sampling) to identify and rank the importance of parameters. The analysis showed that outputs were sensitive to solubility and diffusivity within the stratum corneum, to stratum corneum thickness, and to the volume of gas in the sampling chamber above the skin. We conclude that ethanol transport through the skin is primarily governed by the washin and washout of ethanol through the stratum corneum. The dynamics can be highly variable from subject to subject because of variability in the physical properties of the stratum corneum.
Anderson
Joseph C
JC
Department of Medicine, Division of Pulmonary and Critical Care Medicine, Univ. of Washington, Seattle, WA 98195-6522, USA. clarkja@u.washington.edu
Hlastala
Michael P
MP
D002492:Central Nervous System Depressants / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D004058:Diffusion; D004817:Epidermis / Q000033:anatomy & histology / Q000737:chemistry / Q000378:metabolism; D000431:Ethanol / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D008954:Models, Biological; D015203:Reproducibility of Results; D012867:Skin / Q000033:anatomy & histology / Q000737:chemistry / Q000378:metabolism*; D012995:Solubility; D013696:Temperature; D014867:Water / Q000032:analysis
D002492:Central Nervous System Depressants; D014867:Water; D000431:Ethanol