Drug Evaluation in the Plasmodium Falciparum-Aotus Model

Infections of two strains of Plasmodium falciparum, Uganda Palo Alto (chloroquine sensitive) or Vietnam Smith (chloroquine resistant), in Aotus trivirgatus, were used to evaluate the blood schizonticidal and curative activity of experimental antimalarial drugs. WR 250548, stereoisomers of floxacrine...

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Bibliographic Details
Main Author: Rossan, Richard N
Format: Report
Language:English
Subjects:
ANTIMALARIALS
AS870
BLOOD
CHLORIDES
CHLOROQUINE
DOSAGE
Floxacrine
INFECTIOUS DISEASES
ISOMERS
ORAL DOSAGE
OWL MONKEYS
PARASITEMIAS
PE62770A
Pharmacology
PLASMODIUM FALCIPARUM
RATIOS
SODIUM
STRAINS(BIOLOGY)
TEST AND EVALUATION
VEINS
VIETNAM
WR-250547 Antimalarials
WR-250548 Antimalarials
WU028
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Summary:Infections of two strains of Plasmodium falciparum, Uganda Palo Alto (chloroquine sensitive) or Vietnam Smith (chloroquine resistant), in Aotus trivirgatus, were used to evaluate the blood schizonticidal and curative activity of experimental antimalarial drugs. WR 250548, stereoisomers of floxacrine, administered in combination each at doses of 0.5 or 1.0 mg base per kg (x 3 days) cleared and/or cured Vietnam Smith infections. Other doses ratios were equally effective indicating a potentiating effect of WR 250547 for WR 250548. Three 9-phenanthrenemethanols were evaluated against Vietnam Smith infections: neither the chloride or biquinate salts of halofantrine were effective, at the doses used; WR 122455 cured these treatment failures as well as primary infections. A single intravenous dose of 2-fluoro-1-histidine of 50.0 or 100.0 mg base per kg had no effect upon Uganda Palo Alto strain parasitemias. When 2-iodo-histidine was administered, either as a single intravenous dose of 200.0 or 400.0 mg base per kg or as three oral doses of 100.0 mg base per kg, no antimalarial activity was observed. Sodium artesunate, administered intravenously at a dose of 30.0 mg per kg (x 2 days), temporarily suppressed Uganda Palo Alto parasitemia. Trails are in progress to adapt the UNC-W2-MEF clone of the CDC Indochina III strain of P. falciparum to Aotus.