title: [Affinity of Luliconazole to Keratin Prepared from Healthy Human Nailand Porcine Hoof].
abstract: Luliconazole (LLCZ), an imidazole derivative with a broad spectrum of potent antifungal activity especially for T. rubrum and T. mentagrophytes, is under development as a new drug for treatment of tinea unguium.　It is well known that curative effect of an antifungal agent in dermatophytosis is affected by the pharmacokinetics of an agent at the infection loci as well as its antifungal activity, but there is no report about the affinity of LLCZ to nail keratin. We studied LLCZ affinity to keratin powder prepared from healthy human nail and porcine hoof. The LLCZ adsorbed to keratin preparations was washed with phosphate buffer, and its concentration in the buffer supernatant was measured by HPLC. Antifungal titer of the supernatant was also biologically confirmed by disk diffusion assay. Adsorption rate of LLCZ was 80% or more, and LLCZ was gradually liberated into washing buffer. Cumulative liberation rate in 10 times repeated washing against initially adsorbed drug amount was 47.4% for keratin from human nail and was either 52.5% or 50.8% (depending on the LLCZ concentration) for keratin from porcine hoof. The supernatant showed antifungal potential to T. rubrum. These results indicate that LLCZ applied to the nail surface is fully adsorbed to nail keratin and gradually liberated from it. The nail keratin could function as drug reservoir to supply biologically active LLCZ to the nail tissue region of infection loci. The LLCZ delivered to the loci would exert its antifungal potential on tinea unguium. This study also suggests the versatility of porcine hoof powder as an alternative to human nail keratin preparation for non-clinical study.
authors.affiliation: Nihon Nohyaku Co., Ltd.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hasuko
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Toga
authors.forename: Toshiya
authors.initials: T
authors.lastname: Tsunemitsu
authors.forename: Takahiro
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Koga
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hirano
authors.forename: Ryoji
authors.initials: R
authors.lastname: Tsuboi
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D006724:Hoof and Claw / Q000737:chemistry* / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D007093:Imidazoles / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D007633:Keratins / Q000302:isolation & purification* / Q000378:metabolism*; D009262:Nails / Q000737:chemistry* / Q000378:metabolism / Q000382:microbiology; D014009:Onychomycosis / Q000188:drug therapy / Q000382:microbiology; D011485:Protein Binding; D013552:Swine; D014249:Trichophyton / Q000187:drug effects
chemical_list: D000935:Antifungal Agents; D007093:Imidazoles; D007633:Keratins; C112528:luliconazole