title: Transungual delivery of ketoconazole using novel lacquer formulation.
abstract: Onychomycosis, a common fungal infection of the nail, can have a substantial impact on quality of life. The success of topical therapy for onychomycosis depends on effective penetration, which can be enhanced using an appropriate delivery method. This study evaluated the effectiveness of a novel topical lacquer on enhancing [(14)C]-ketoconazole penetration by comparing nail absorption, nail distribution, and nail penetration of [(14)C]-ketoconazole dissolved in the novel lacquer versus a commercial ketoconazole cream. Using the in vitro finite dose model, the formulations were applied daily to human nail plates for 7 days. Drug absorption was measured by monitoring rate of appearance in each nail layer and the supporting bed. After the multiple day treatment, cumulative concentrations of ketoconazole formulated in novel lacquer in the deep nail layer and the nail bed were significantly greater than cumulative concentrations of commercial ketoconazole (p<0.05), as well as several orders of magnitude greater than the minimal inhibitory concentration (MIC) deemed necessary to inhibit the growth of causative dermatophytic and yeast species. These results suggest that this novel ketoconazole lacquer has the potential to be an effective topical treatment for onychomycosis.
authors.affiliation: Dermatology Department, University of California, San Francisco, 90 Medical Center Way, Surge Building, Room 110, San Francisco, CA 94143-0989, USA. Electronic address: farhaanhafeez@gmail.com.
authors.forename: Farhaan
authors.initials: F
authors.lastname: Hafeez
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Hui
authors.forename: Audris
authors.initials: A
authors.lastname: Chiang
authors.forename: Sidney
authors.initials: S
authors.lastname: Hornby
authors.forename: Howard
authors.initials: H
authors.lastname: Maibach
mesh_terms: D000935:Antifungal Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D007654:Ketoconazole / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D007764:Lacquer; D009262:Nails / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology; D014009:Onychomycosis / Q000188:drug therapy / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D007654:Ketoconazole
keywords: Human nail; In vitro; Ketoconazole; MIC; Onychomycosis; Topical formulation