The influence of bifonazole and other azoles on the leukotriene-metabolism of human neutrophil granulocytes (PMN) was investigated. The cells were stimulated with the Ca-ionophore A23187 over 15 minutes in the presence of the azoles. Subsequently the supernatants were analyzed for their leukotriene content by reversed-phase HPLC. In order to confirm that the observed effects are not due to cytotoxic phenomena tests were performed to evaluate the viability of the granulocytes. The chemotactic active leukotriene B4 (LTB4) and its inactive omega-metabolites were detected and quantified by HPLC analysis. The results clearly demonstrated that bifonazole inhibited the omega-oxidation already at concentrations as low as 0.5 microgram ml-1. As a consequence the LTB4-level became elevated. At concentrations up to 64 micrograms ml-1 bifonazole totally blocked the formation of leukotrienes in human granulocytes. Identical experiments were performed with other azoles and with various anti-inflammatory drugs just to have a comparison with bifonazole. It is evident that bifonazole in addition to its well known antimycotic action shows a unique modulation of the leukotriene-metabolism, which is important for its anti-inflammatory potency.

Antifungal Agents↗

PubMedDate not supplied

Experimental in vitro and in vivo comparison of modern antimycotics.

Studies were carried out with the current leading antimycotic agents, using identical test methods, to compare their activity in vitro and in animal in vivo experiments. In the broth dilution test, the minimum inhibitory concentrations against approximately 50 strains of the most important species of yeasts, dermatophytes and moulds were determined using different culture media. Efficacy against yeasts was examined in experimentally-induced candidosis in mice treated orally, and against dermatophytes in experimentally-induced trichophytia in guinea pigs receiving topical treatment. The results showed that the imidazole derivatives studied can be regarded as true broad-spectrum antimycotics, and clotrimazole, in particular, had a well-balanced overall effect. The significance of the experimental data with respect to therapeutic efficacy in man in various indications is discussed.

Administration, Oral↗