Drug Evaluation in the Plasmodium Falciparum-Aotus Model
Abstract
Infections of the pyrimethamine resistant Vietnam Smith strain of Plasmodium falciparum in the Panamanian Owl Monkey (Aotus trivirgatus) were used to evaluate the activity of four folic acid inhibitors. As expected, there was cross resistance to pyrimethamine (WR 002978), proguanil (WR 003019) and cycloguanil (WR 005473). A proguanil analog (WR 250417), however, had significant antimalarial activity. A 3-day dosage of 1.0 mg/kg cured 3 of 7 infections, 10.0 mg/kg cured 6 of 8 infections, and 50.0 mg/kg cured 4 of 4 infections. Trials were initiated to reverse, in vivo, chloroquine resistance in infections with the Vietnam Smith and Smith/RE strains (chloroquine resistant) by the co-administration of calcium channel blockers plus chloroquine. These trials were based upon the reports of in vitro reversal of chloroquine resistance. Six calcium channel blockers, or similar acting drugs were tested. In 26 primary treatments with a channel blocker plus chloroquine, parasitemias were cleared in two monkeys each treated with WR255694, verapamil. Nifedipine, WR 255695, cured four infections. WR 256287 cured two infections. It is difficult to assign cure to either drug action or acquired immunity, and probably resulted from a combination of both. (AW)
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 1988
- Accession Number
- ADA212678
Entities
People
- Richard N. Rossan