title: In vivo activity and metabolic fate of 2-(2,3,3-triiodoallyl)tetrazole (ME1401), a novel antifungal agent.
abstract: 2-(2,3,3-Triiodoallyl)tetrazole (ME1401), a novel antifungal agent, showed therapeutic effectiveness in topical treatment of experimental dermal infections with Trichophyton mentagrophytes and Candida albicans in guinea-pigs. Addition of diethyl sebacate to the ME1401 preparations increased its in vivo antifungal activity and its penetration into the skin. When the estimation of efficacy of treatment with active formulations was made on the basis of skin lesion and the rate of negative skin cultures in comparison with those for infected, untreated or placebo-treated controls, the in vivo activity of 0.5% ethanol tincture or gel of ME1401 was comparable to that of reference antimycotic drugs such as clotrimazole, haloprogin and others. Pharmacokinetic studies in the experimental animals demonstrated that ME1401 was unstable in vivo, being readily converted to an active metabolite 2-(3-iodopropargyl)tetrazole (CN144) first and then to 2-propargyltetrazole (CN151). CN144 showed potent in vitro and in vivo antifungal activities, while the in vitro activity of CN151 was negligible.
authors.affiliation: Central Research Laboratories, Meiji Seika Kaisha, Ltd., Yokohama, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Fukuyasu
authors.forename: Y
authors.initials: Y
authors.lastname: Orikasa
authors.forename: F
authors.initials: F
authors.lastname: Kai
authors.forename: S
authors.initials: S
authors.lastname: Inouye
authors.forename: I
authors.initials: I
authors.lastname: Kitasato
authors.forename: H
authors.initials: H
authors.lastname: Yamaguchi
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000378:metabolism / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology*; D002177:Candidiasis / Q000188:drug therapy; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005658:Fungi / Q000187:drug effects; D006168:Guinea Pigs; D008297:Male; D008826:Microbial Sensitivity Tests; D012869:Skin Absorption; D013552:Swine; D013556:Swine, Miniature; D013777:Tetrazoles / Q000378:metabolism / Q000494:pharmacology*; D014005:Tinea / Q000188:drug therapy
chemical_list: D000935:Antifungal Agents; D001393:Azoles; D013777:Tetrazoles; C050462:2-(2,3,3-triiodoallyl)-2H-tetrazole