Pharmacokinetic studies following systemic and topical administration of [14C]bifonazole in man

[14C]Bifonazole (1-[(4-Biphenylyl)-phenylmethyl]-1H-imidazole, Bay h 4502, Mycospor) was administered systemically (i.v.) and topically (dermally) in different formulations to a total of 17 volunteers. In the serum, the concentrations of total radioactivity and of the unchanged drug were determined by liquid scintillation counting techniques and by thin-layer densitometry, respectively. Urine and feces were collected and radioassayed. The extent of percutaneous absorption was calculated. In addition, distribution of the unchanged drug in the layers of the skin was studied radiometrically in three patients. After intravenous administration, bifonazole was eliminated from the serum largely in metabolized form. The half-lives of elimination of the radioactivity from the serum were approximately 7 and 42 h. Within 5 days 45% of the dose was excreted with the urine, and 39% with the feces. After topical application to healthy skin areas, under occlusive conditions, less than 1% of bifonazole was absorbed percutaneously from a 1% solution or cream, and the amount absorbed was excreted with the urine and the feces in approximately the same proportions as after i.v. administration. Following administration of the drug to inflamed skin, the proportion absorbed was 3 to 4% of the dose administered and thus higher than after application to normal skin. Studies on depth localization showed that the drug has a high capacity for skin penetration. Even in the lower layers of the epidermis, bifonazole was present in amounts several times as high as the minimum inhibitory concentrations for dermatophytes measured in vitro.