Drug Evaluation in the Plasmodium Falciparum-Aotus Model
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 Smith/RE 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 14, 1990
- Accession Number
- ADA235726
Entities
People
- Richard N. Rossan