title: Effect of hydration on the permeation of ketoconazole through human nail plate in vitro.
abstract: The impact of hydration on the permeation of the antifungal drug, ketoconazole, through excised human nails in vitro was evaluated in diffusion cell studies. Nails treated with [(3)H]ketoconazole solvent-deposited onto the dorsal surface were maintained in incubators at 32 degrees C and exposed sequentially to relative humidities (dorsal side) of 15, 40, 80 and 100% over a period of 40 days. The ventral side was bathed in a pH 7.4 phosphate buffer. Ascending and descending humidity regimens were tested. Increasing the ambient RH from 15 to 100% enhanced permeation of radiolabel associated with [(3)H]ketoconazole by a factor of three. Diffusivities estimated from these data and the associated nail water contents (estimated in a separate study) can be described by a free volume theory. Therefore, formulations or treatments, which increase nail hydration, have potential to improve topical therapy for onychomycosis, if a favorable balance between drug delivery and growth conditions for the dermatophytes can be achieved.
authors.affiliation: James L. Winkle College of Pharmacy, University of Cincinnati, OH 45267, USA.
authors.forename: Hemali B
authors.initials: HB
authors.lastname: Gunt
authors.forename: Gerald B
authors.initials: GB
authors.lastname: Kasting
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D004058:Diffusion; D006801:Humans; D006813:Humidity; D007654:Ketoconazole / Q000737:chemistry / Q000494:pharmacology*; D009262:Nails / Q000187:drug effects*; D010539:Permeability / Q000187:drug effects; D013997:Time Factors; D014316:Tritium / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D000935:Antifungal Agents; D014867:Water; D014316:Tritium; D007654:Ketoconazole