title: The effects of skin disease on the penetration kinetics of hydrocortisone through canine skin in vitro.
abstract: This study investigated the effects of allergic skin disease on the penetration kinetics of hydrocortisone through canine skin in vitro. Full-thickness lesional and nonlesional (normal) skin was removed from the dorsal lumbosacral and dorsocaudal thoracic regions, respectively, of five canine cadavers. The dogs were suspected of having flea allergy dermatitis based on their distribution and types of skin lesions. Nonlesional skin was confirmed to be histologically normal, and the histopathology of the lesional skin was consistent with allergic dermatitis. Excised skin was clipped, mounted in Franz-type diffusion cells, and the transdermal penetration of a saturated, radiolabelled hydrocortisone solution was measured over 30 h. When the penetration data for all five dogs were pooled, a restricted (or residual) maximal likelihood mixed model predicted that the permeability coefficient and pseudosteady-state flux of hydrocortisone was more than twice as great (95% confidence interval 1.55-2.71 times as great; P < 0.0001) through lesional compared with nonlesional skin. There was no significant difference in the lag time for hydrocortisone penetration through lesional compared with nonlesional skin of the dogs. This study has confirmed that the transdermal penetration of hydrocortisone may be altered, typically increased twofold, but could be as high as 10-fold, through lesional compared with nonlesional skin of dogs with suspected flea allergy dermatitis. This is likely to be affected by variables such as disease severity, concurrent infections and interindividual differences in skin characteristics.
authors.affiliation: School of Veterinary Science, The University of Queensland, Brisbane, Qld 4072, Australia. liisa.ahlstrom@sydney.edu.au
authors.forename: Liisa A
authors.initials: LA
authors.lastname: Ahlstrom
authors.forename: Sheree E
authors.initials: SE
authors.lastname: Cross
authors.forename: Paul C
authors.initials: PC
authors.lastname: Mills
mesh_terms: D000042:Absorption / Q000502:physiology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000493:pharmacokinetics*; D017449:Dermatitis, Allergic Contact / Q000378:metabolism / Q000662:veterinary*; D004283:Dog Diseases / Q000378:metabolism*; D004285:Dogs; D005260:Female; D006854:Hydrocortisone / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D016013:Likelihood Functions; D008297:Male; D010539:Permeability; D005423:Siphonaptera / Q000276:immunology; D012867:Skin / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D006854:Hydrocortisone