Activity of a new liposomal formulation of amphotericin B against two strains of Leishmania infantum in a murine model.
The efficacy of a new liposomal formulation of amphotericin B was compared to that of amphotericin B deoxycholate (Fungizone) in a murine model of visceral leishmaniasis induced by Leishmania infantum. Median effective doses (ED50) were determined with two different strains: strain 1 was obtained from an untreated patient, and strain 2 was obtained from a patient who had received 12.5 g of amphotericin B over 3 years. BALB/c mice were infected intravenously on day 0 with promastigotes and then treated on days 14, 16, and 18 (strain 1) or on days 21, 23, and 25 (strain 2) with the liposomal formulation of amphotericin B (five doses were tested for each strain: 0.05, 0.1, 0.5, 0.8, and 3 mg/kg of body weight) or with conventional amphotericin B (four doses were tested for each strain: 0.05, 0.1, 0.5, and 0.8 mg/kg). Mice in the control group received normal saline solution. The liposomal amphotericin B formulation was about three times more active than the conventional drug against both strains. ED50 of the liposomal formulation were 0.054 (strain 1) and 0.194 (strain 2) mg/kg. ED50 of conventional amphotericin B were 0.171 (strain 1) and 0.406 (strain 2) mg/kg. Determination of drug tissular levels, 3 days after the last drug administration, showed a drug accumulation in hepatic and splenic tissues much higher after administration of liposomal amphotericin B than after conventional amphotericin B. A lack of toxicity was noted in all groups treated with the liposomal formulation.
Paul
M
M
Laboratoire de Pharmacotechnie, Service Pharmacie, CHU H. Mondor, Creteil, France. alastier@micronet.fr
Durand
R
R
Fessi
H
H
Rivollet
D
D
Houin
R
R
Astier
A
A
Deniau
M
M
D000666:Amphotericin B / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical; D005069:Evaluation Studies as Topic; D018314:Leishmania infantum / Q000187:drug effects* / Q000378:metabolism; D007896:Leishmaniasis / Q000188:drug therapy / Q000469:parasitology; D008081:Liposomes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
D000900:Anti-Bacterial Agents; D008081:Liposomes; D000666:Amphotericin B