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No effect of albumin on the dermal absorption rate of hydrocortisone 21-butyrate, permethrin or diflunisal in the isolated, single-pass perfused rabbit ear.

Rabbit ears were single-pass perfused with a buffer solution containing either 6% hetastarch or 5% bovine serum albumin. Hydrocortisone 21-butyrate (5 mM), diflunisal (17 mM) or permethrin (33 mM) was added to isopropyl myristate with 5% polyethylene, and applied to about 40% of the epithelial surface area of the ear. Hydrocortisone 21-butyrate or permethrin were not found in the effluent with hetastarch or albumin. Following cutaneous ester hydrolysis, the appearance rate of hydrocortisone was about 4 pmol/min per cm2 in the hetastarch- or the albumin-containing buffer solution. No hydrolysis of permethrin was detected; the appearance rate of 3-phenoxybenzyl alcohol with 3-phenoxybenzoic acid corresponded to the absorption rate of the substrate impurities. During ex vivo perfusion of intact skin, serum albumin in the perfusion fluid may not enhance the appearance rate of xenobiotics in the effluent following dermal application when the distribution coefficient n-octanol/water is > 2,000 or when the xenobiotic is ionized at physiological pH. In general, for all substances investigated with our perfusion model thus far, the appearance rates decreased with rising distribution coefficient (n-octanol/buffer pH 7.4). High lipophilicity hinders the release from isopropyl myristate and the penetration through the skin.