Accession Number:

ADA210494

Title:

Drug Evaluation in the Plasmodium Falciparum-Aotus Model

Descriptive Note:

Annual rept. 15 May 1988-14 May 1989

Corporate Author:

GORGAS MEMORIAL INST OF TROPICAL AND PREVENTIVE MEDICINE INC BETHESDA MD

Personal Author(s):

Report Date:

1989-06-14

Pagination or Media Count:

48.0

Abstract:

Blood-induced infections of the multidrug resistant Vietnam SmithRE strain of Plasmodium falciparum in Aotus lemurinus lemurinus were used as a model for antimalarial drug evaluation studies. Trials to reverse chloroquine resistance in vivo with WR 256287, an analog of tiapamil, plus chloroquine, resulted only in suppression of parasitemia. Similar trials with WR 149244, desipramine, plus chloroquine, were partially successful in that primary treatments cleared parasitemias, but infections were not cured. Parasite clearance is the first indication that in vivo reversal of chloroquine-resistance may eventually be feasible in human patients. However, the toxicity of the combined drug regime must be ameliorated. Four derivatives of artemisinin, the active antimalarial principal of ginghao were evaluated for their antimalarial activity in the P. falciparum - Aotus model. Two of these drugs, WR 255131 arteether and WR 254986 artemether, the two water soluble derivatives evaluated were WR 255663 artelinate and WR 256283 artesunate. These drugs were administered intravenously or intramuscularly, at doses of 64.0 and 96.0 mgkg X3, q.6h, q.12h, or q.24h. Toxicity has been associated with these regimens. To date, artelinate cleared parasitemias in 14 of 15 treatments, and cured 4 of 15 infections. Artesunate cleared parasitemias in 3 of 3 treatments, and cured 1 of 3 infections. Keywords Antimalarials.

Subject Categories:

  • Pharmacology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE