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Activity of amphotericin B cholesterol dispersion (Amphocil) in experimental visceral leishmaniasis.

Abstract：

: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.

journal_name

Antimicrob Agents Chemother

journal_title

Antimicrobial agents and chemotherapy

authors

Berman JD,Ksionski G,Chapman WL,Waits VB,Hanson WL

doi

10.1128/aac.36.9.1978

subject

Has Abstract

pub_date

1992-09-01 00:00:00

pages

1978-80

issue

9

eissn

0066-4804

issn

1098-6596

journal_volume

36

pub_type

杂志文章

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