Testing Experimental Compounds against Leishmaniansis in Laboratory Animal Model Systems
Annual summary rept. 15 Dec 1983-1 Nov 1984
CORNELL UNIV MEDICAL COLL (WEILL) NEW YORK
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Pentostam Dose Responses for L. donovani, L. m. mexicana, and L. b. guyanensis have been determined in BALBc mice using amastigotes A, primary culture promastigotes PCP, and subcultured promastigotes SP. In each test system, PCP are more resistant to treatment than are A or SP. This is biologically significant, since PCP are equivalent to the ineffective stage from sandflies. The data also show that Pentostam causes improvement and parasitological cures in WRAIR primary hamster, secondary BALBc, and tertiary owl monkey test systems at doses and regimes equivalent to those used to treat humans. The validity of each of these models in drug screening to predict the outcome in human infections is established. Seven of 10 WRAIR 1984 compounds suppress L. donovani 79 to 94 at the MTD MTD2, and MTD4. It is highly probable they will be competitive with Pentostam.