Ketoconazole in cutaneous leishmaniasis

Importance and Role of Sterols in Fungal Membranes

“…are 24-methylene-7-dehydrocholesterol, 24-methylenelathosterol, 24 (18)-dehydroergosterol and ergosterol, all 24-alkylated sterols (Holz 1985). That the latter sterols playa role in these protozoa can be deduced from the fact that the 14a-demethylase inhibitors ketoconazole (Berman et al 1986) and itraconazole (Hart et al 1989) inhibit ergosterol synthesis in Leishmania amastigotes and proved to have clinically useful antileishmanial activities (Weinrauch et al 1987;Borelli 1987). Although the Leishmania surface membrane must present "refractory" properties to withstand the lysosomal environment in the host macrophage, its chemical composition does not indicate a rigidity similar to that of the fungal cell wall.…”

Challenges and new discoveries in the treatment of leishmaniasis

“…However, other derivatives were found ineffective or toxic. 13,[35][36][37] The mechanism of action of ketaconazole against Leishmania promastigotes is the same as for Candida albicans, i.e., interference with membrane permeability (cytochrome P450) secondary to loss of desmethyl sterols and accumulation of 14a-methyl sterols. These sterols have a detrimental effect on the membrane permeability and hence on the viability of the organism.…”

“…Although more than 20 drugs have been studied or tried to treat leishmaniasis, only a few have been found effective. 13,[32][33][34][35][36][37][38][39][40][41] Allopurinol Allopurinol was the first oral drug. This hypoxanthine analogue inhibits purine catabolism in mammalian cells and purine anabolism in Leishmania.…”

A Species-Specific Approach to the Use of Non-Antimony Treatments for Cutaneous Leishmaniasis

“…Limited clinical reports suggest that ketoconazole cures CL in Nicaragua, Israel, Algeria, Saudi Arabia, and Ethiopia. [32][33][34][35][36] Decreased cure rates have been noted in limited reports from Belize, 53 although species identification beyond the complex level was not performed in most cases. For this reason, close follow-up of CL cases is necessary to monitor treatment response so that an alternative agent can be used if necessary.…”