PRECLINICAL DATA AND MODE OF ACTION OF AMOROLFINE

Amorolfine is an antifungal showing activity against fungi pathogenic to plants, animals and humans. Amorolfine possesses a broad antifungal spectrum including dermatophytes, yeasts, dimorphic fungi and moulds and is not only fungistatic but fungicidal against most species. Amorolfine interferes with ergosterol biosynthesis at two steps: the DELTA-14 reduction and the DELTA-7-8 isomerisation. As a consequence of this inhibition the DELTA-14 sterol ignosterol is accumulated in the cell membrane and ergosterol is depleted. The cell wall thickness is significantly increased and chitin deposits are included inside and outside. In experimental models of systemic mycosis amorolfine shows no significant activity. This lack of systemic activity may be due to strong protein binding and/or rapid metabolism. In models of superficial fungal infection-trichophytosis and vaginal candidosis-amorolfine has a high activity. On a concentration basis amorolfine is more effective in trichophytosis than naftifine and all azoles tested. Amorolfine clears mycotic foci of trichophytosis in the guinea pig in 10 days, while none of the azoles is able to cure these animals. Tolciclate and terbinafine are the only other substances with a curative effect in these experiments. Amorolfine has a long retention time in the horny layer of the skin. In vaginal candidosis 0.1% amorolfine clears the vagina of viable candida cells in rats.