THERAPY OF VISCERAL LEISHMANIASIS DUE TO LEISHMANIA-INFANTUM - EXPERIMENTAL ASSESSMENT OF EFFICACY OF AMBISOME

The tolerance and efficacy of amphotericin B (AmB) deoxycholate (Fungi zone) were compared with those of liposomal AmB (AmBisome) in a murine model of visceral leishmaniasis induced by Leishmania infantum. Contr ol groups consisted of untreated mice and mice treated with a pentaval ent antimonial (Glucantime). BALB/c mice were infected intravenously o n day 0 with 10(7) promastigotes of L. infantum and then treated from day 7 to 17 (early treatment group) or from day 60 to 70 (delayed trea tment group). The pentavalent antimonial was administered daily by int raperitoneal injection, whereas AmB formulations were administered int ravenously on alternate days. On days 20, 60, and 120 (early treatment group) and on days 72 and 125 (delayed treatment group), parasite bur dens in the liver, spleen, and lungs were determined by subculturings using a microtitration method. A dose range study showed that administ ration of AmBisome at the well-tolerated doses of 5 or 50 mg/kg of bod y weight completely eradicated the parasites from the tissues. At 0.8 mg/kg, AmBisome proved more efficacious than AmB deoxycholate administ ered at the same dose. We also compared the levels of AmB deoxycholate and AmBisome in plasma and tissue. Mice treated with AmBisome had lev els of AmB in tissue much higher than did AmB deoxycholate-treated mic e with persistent detectable levels 14 weeks after treatment. These re sults seem to account for the remarkable efficacy of the liposomal for mulation of AmB in the treatment of visceral leishmaniasis due to L. i nfantum.