Standard
therapy of human
visceral leishmaniasis with parenteral pentavalent antimonial agents is generally curative but has the disadvantages of a 28-day treatment course, occasional treatment failures, and toxicity. The antifungal and antileishmanial agent
amphotericin B has been complexed with
lipids to develop a less toxic formulation of
amphotericin B. Because
lipid particles are phagocytized by the reticuloendothelial system,
lipid-associated
amphotericin B should be concentrated in infected macrophages and be very effective against
visceral leishmaniasis. One formulation,
amphotericin B cholesterol dispersion (ABCD) (
Amphocil), was tested for antileishmanial activity in Leishmania donovani-infected hamsters. In the first experiment, hamsters were infected, administered with the
drug 3 days later, and then sacrificed after a further 4 days. ABCD (dose needed to suppress 99% of hepatic parasites compared with controls [SD (99)], 0.4 mg/kg of
body weight) was 15 times as effective as conventional
amphotericin B [SD (99), 6.0 mg/kg]. Pentavalent
antimony in the form of
meglumine antimonate had an SD (84) of 416 mg/kg. In a second experiment in which animals were allowed to become more heavily infected, the
drug was administered 10 days after
infection and the animals were sacrificed after a further 2, 7, or 11 days. ABCD was approximately four times as active as conventional
amphotericin B. These experiments suggest that ABCD is at least four times as active as conventional
amphotericin B against
visceral leishmaniasis and that clinical trials are warranted.