Terbinafine

Abstract Terbinafine is a newly developed oral and topical antifungal agent in the allylamine class of antifungal compounds (Petranyi et al, 1984). Discovered in 1983, it is closely related to naftifine. Terbinafine became available in Europe in 1991, and in 1996 in the United States. Terbinafine is the only oral allylamine available in the United States and is used largely for the treatment of superficial fungal infections, especially those due to dermatophytes. There has been significant interest in developing the drug for the treatment of deep mycoses, either alone or in combination, for disorders such as cryptococcosis, invasive aspergillosis, and other mould infections, but there are only scant clinical data evaluating its efficacy in these settings. Terbinafine is a very valuable antifungal drug for the treatment of superficial fungal infections, and has potential as an adjunctive agent in the treatment of selected deep mycoses. Terbinafine has a unique mechanism of action among the antifungal agents (Petranyi et al, 1984; Balfour and Faulds, 1992), inhibiting the synthesis of ergosterol, a key sterol component in the plasma membrane of the fungal cell. Terbinafine inhibits squalene epoxidase, the enzyme which catalyzes the conversion of squalene to squalene-2,3 epoxide, a precursor of lanosterol, which in turn is a direct precursor of ergosterol (Ryder and Dupont 1985; Birnbaum, 1990). A deficiency of ergosterol is detrimental to the integrity of the cell membrane resulting in a fungistatic effect similar to that seen with the azole antifungal compounds. In addition to this action, terbinafine also causes excessive intracellular accumulation of squalene, which is believed to exert a further toxic effect on susceptible fungal cells, thereby exerting a fungicidal effect (Ryder, 1992).