Leishmania donovani: Oral efficacy and toxicity of formycin B in the infected hamster |
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Authors: | J.D. Berman C.M. Keenan S.R. Lamb W.L. Hanson V.B. Waits |
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Affiliation: | Department of Parasitology, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, D.C. 20012, U.S.A.;Division of Pathology, Walter Reed Army Institute of Research, Washington, D.C. 20012, U.S.A.;Department of Parasitology, College of Veterinary Medicine, University of Georgia, Athens, Georgia, U.S.A. |
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Abstract: | Formycin B, a structural analog of inosine, was evaluated as an orally administrable antileishmanial agent. Against Leishmania donovani in hamsters, it achieved an 85–92% reduction in numbers of parasites in livers of infected animals after oral administration at 13 mg/kg/day for 4 days. Its efficacy by oral administration was approximately four to eight times that by intramuscular administration and four times that of the positive control drug Glucantime by intramuscular administration. The levels of formycin B in serum after the final oral administration of 26 mg/kg/day were 1.4 μg/ml at 1 hr and 0.3 μg/ml at 2 hr. The concentration in liver was greater (9.0 μg/ml at 1 hr) and declined more slowly. With this latter dosage or with 104 mg/kg/day there was no acute toxicity of formycin B to bone marrow or formed elements of the blood. The only statistically significant toxicity to the liver was a doubling of serum total bilirubin levels. Comparison of the in vivo efficacy of formycin B against L. donovani to the mild acute toxicity of the drug suggests that formycin B has potential as an oral agent against visceral leishmaniasis. |
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Keywords: | Protozoa parasitic Hemoflagellate Formycin B Purine analogs Hamster Liver toxicity Treatment |
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