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Accession Number:
ADA235726
Title:
Drug Evaluation in the Plasmodium Falciparum-Aotus Model
Descriptive Note:
Annual rept. 15 May 1989-14 May 1990
Corporate Author:
GORGAS MEMORIAL INST OF TROPICAL AND PREVENTIVE MEDICINE INC BETHESDA MD
Report Date:
1990-06-14
Pagination or Media Count:
57.0
Abstract:
The purpose of this contract is to evaluate experimental antimalarial drugs, singly or in combination, against trophozoite-induced infections of Plasmodium falciparum in Aotus lemurinus lemurinus, the Panamanian owl monkey. The Vietnam SmithRE strain was used and is resistant to maximally tolerated doses of chloroquine, pyrimethamine, and quinine. Four derivatives of artemisinin, the active antimalarial principal of the Chinese herb qinghao, were selected for evaluation in the P. falciparum - Aotus model. Two of these derivatives, WR 255131 arteether and WR 254986 artemether are oil soluble the water soluble derivatives are wr 255663 artelinate and WR 256283 artesunate. Drugs were administered intramuscularly, q.12h.x3. The water soluble, artemisinin derivatives - artesunate and artelinate - effectively cleared parasitemias, but did not cure infections. Additional experiments were initiated to reverse chloroquine-resistance in vivo by the concomitant administration of chloroquine or quinine and a neuroleptic phenothiazine. Chlorpromazine or prochlorperazine, plus chloroquine, may be effective in curing human infections of chloroquine-resistant P. falciparum strains.
Distribution Statement:
APPROVED FOR PUBLIC RELEASE
