Disposition of the Antimalarial, Mefloquine, in the Isolated Perfused Rat Liver
Abstract
Mefloquine is a relatively new antimalarial compound that is highly effective against chloroquine-resistant Plasmodium falciparum malaria. The pharmacokinetics of mefloquine have been studied in dogs 1, rats 2 and humans 1, 3-6. Mefloquine exhibits a large volume of distribution, is concentrated in soft tissues, is metabolized slowly, and undergoes considerable biliary excretion in vivo 1-3. Mefloquine also inhibits hepatic metabolism of aminopyrine in vitro in rat microsomes 7. Therefore, to investigate more fully the hepatic handling of mefloquine, we have chosen the isolated perfused rat liver (IPRL) preparation. This experimental model excludes the influence of other organs and routes of elimination present in the intact animal and has been of value in studies of the disposition of a number of compounds, e.g. cimetidine, propranolol, suramin and the antimalarial primaquine 8-11. Reprints.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 1988
- Accession Number
- ADA201765
Entities
People
- Lawrence Fleckenstein
- Lisa A. Shipley
- Melvin H. Heiffer
- Michael D. Coleman
Organizations
- Walter Reed Army Institute of Research