LIPID FORMULATIONS OF AMPHOTERICIN-B IN THE TREATMENT OF EXPERIMENTALVISCERAL LEISHMANIASIS DUE TO LEISHMANIA-INFANTUM

Despite significant antileishmanial activity of amphotericin B (AmB) i n vitro, the use of the deoxycholate formulation (Fungizone(R)) is lim ited because of serious side effects. Lipid formulations of AmB have b een proposed to reduce this toxicity. We compared the tolerance and ef ficacy of the conventional AmB prepared with deoxycholate, AmB emulsif ied in Intralipid(R) 20%, amphotericin B lipid complex (Abelcet(R)), a nd liposomal AmB (AmBisome(R)) in a murine model of visceral leishmani asis induced by Leishmania infantum. Control groups included untreated mice and mice treated with the pentavalent antimonial (Glucantime(R)) . Balb/C mice were infected intravenously on day 0 with 10(7) promasti gotes of L. infantum, then treated from days 7 to 17 (early treatment group) or from days 60 to 70 (delayed treatment group). Glucantime(R) was administered daily by intraperitoneal injection, whereas AmB formu lations were administered intravenously on alternate days. On days 20, 60 and 120 in the early treatment group and 72 and 125 in the delayed treatment group, parasite burdens were determined in liver, spleen, a nd lungs by subculturing using a microtitration method. Abelcet(R) (12 mg/kg) and AmBisome(R) (12 mg/kg) completely eradicated the parasites from the tissues. Both of these lipid formulations enabled higher dos ages to be tolerated, and were remarkably more effective than Fungizon e(R) (0.8 mg/kg) and AmB diluted in Intralipid 20% (1.2 mg/kg) in the treatment of murine visceral leishmaniasis due to L. infantum.