Comparative Drug Responses of Sensitive and Resistant Strains of Malaria Parasites Using in Vitro Bioassays and Animal Models for Blood and Tissue Schizontocidal Activity and Mechanism of Reversal of Resistance &Toxicity of Antimalarials.
Abstract
A shorter day treatment regimen of compound WR 238605 for anti-relapse activity has been established using P. cynomolgi B model. This compound is undergoing Phase I clinical trials at Walter Reed. This compound has also been found to show significant blood schizontocidal activity as shown by curative action on blood induced P.cynomolgi B and P.fragile infection. A new anti-relapse therapy for possible use in chloroquine resistant P.vivax areas has been successfully developed in which anti-relapse compound WR 238605 is given with halofantrine as blood schizontocide instead of chloroquine. This will be of potential value for use in chloroquine resistant P.vivax areas. The results also suggest that the two drugs would have synergistic effect as blood schizontocide. An isolate of mefloquine, resistant P.knowlesi has been developed which would be used for mefloquine resistance reversal studies. Three drugs evaluated for resistance reversal potential against multiple drug resistant rodent model did not snow any promising results. Tissue stages of P. cynomolgi have been obtained after successful inoculation of hepatocyte cultures with sporozoites. The cultivation of primary e-e stages will be useful to develop in vitro model for screening of tissue schizontocidal drugs.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 28, 1995
- Accession Number
- ADA293450
Entities
People
- V. P. Kamboj
Organizations
- Central Drug Research Institute