title: Difference in percutaneous absorption and intracutaneous distribution in guinea pigs among topical antifungal drugs (tioconazole solution, tioconazole cream, miconazole nitrate solution and bifonazole solution).
abstract: Tioconazole (TCZ) is an imidazole antifungal agent with broad spectrum activity. Percutaneous absorption and intracutaneous distribution of TCZ solution have been compared with TCZ cream, miconazole nitrate (MCZ) solution and bifonazole (BFZ) solution following a single topical application to abdominal skin of guinea pigs. Following application of TCZ solution, TCZ concentrations in the stratum corneum, epidermis-cutis and subcutaneous tissue were higher than those after TCZ cream application suggesting superior percutaneous penetration after TCZ solution application. The percutaneous penetration after applications of MCZ solution and BFZ solution was comparable to that of TCZ cream, but inferior to that of TCZ solution. TCZ concentrations in the stratum corneum were much higher than those in epidermis-cutis and subcutaneous tissue after applications of both TCZ formulations. The majority of applied TCZ remained in the stratum corneum at high levels for a long duration. TCZ concentrations in the stratum corneum within 24 h after applications of both TCZ formulations were more than several hundred times higher than the minimum inhibitory concentrations against most of the dermatophytes and yeasts. The effectiveness of both TCZ formulations against dermatophytoses may be due to this favorable pharmacokinetic property in the skin tissues, together with its potent antifungal activity. Percutaneous absorption of TCZ after applications of both formulations was negligible suggesting that these treatments are unlikely to produce systemic side effects.
authors.affiliation: Department of Clinical Pharmacology, Pfizer Global R & D, Tokyo Laboratories, Pfizer Japan Inc., Shinjuku Bunka Quint Bldg., 3-22-7 Yoyogi, Shibuya-ku, Tokyo 151-8589, Japan. satoshi.sobue@japan.pfizer.com
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sobue
authors.forename: Kaneo
authors.initials: K
authors.lastname: Sekiguchi
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004304:Dosage Forms; D004334:Drug Administration Schedule; D006168:Guinea Pigs; D007093:Imidazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008825:Miconazole / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012867:Skin / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D004304:Dosage Forms; D007093:Imidazoles; D008825:Miconazole; C036596:bifonazole; C020527:tioconazole