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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Activity of oral drugs against Leishmania tropica in human macrophages in vitro.

Because of the need for orally active antileishmanial agents, orally administrable drugs have sometimes been used to treat human leishmaniases without prior demonstration of efficacy in experimental models. The antileishmanial activity of such agents was tested against Leishmania tropica (a cause of cutaneous leishmaniasis) within human macrophages in vitro. Although trimethoprim + sulfamethoxazole and isoniazid + rifampin have been reported as efficacious orally in certain human studies of cutaneous disease, these drugs were ineffective in vitro (less than or equal to 40% parasite elimination) at peak achievable serum levels. The combination of allopurinol and Pentostam is being tested in humans. In vitro, allopurinol (5 micrograms/ml) augmented the antileishmanial effect of a low concentration of Pentostam (5 micrograms/ml) but not of a higher concentration of Pentostam (20 micrograms/ml). Nifurtimox is a nitrofuran which has questionable activity against human cutaneous disease. Nifurtimox was similarly only 50% effective in vitro at peak achievable serum levels (1.0-3.0 micrograms/ml). However, furazolidone, another orally administered nitrofuran, eliminated 92% of parasites at 1.0 micrograms/ml. Chlorpromazine and quinacrine are concentrated in tissues that are susceptible to infection by Leishmania. Chlorpromazine and quinacrine eliminated only 15% and 35% of organisms in vitro at achievable serum levels (less than or equal to 0.3 microgram/ml), but eliminated virtually all organisms in vitro at possible achievable tissue levels. Both the negative and the positive data of this report may aid in selection of effective orally active agents for in vivo trials.[1]


  1. Activity of oral drugs against Leishmania tropica in human macrophages in vitro. Berman, J.D., Lee, L.S. Am. J. Trop. Med. Hyg. (1983) [Pubmed]
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