Disposition of the Antimalarial, Mefloquine, in the Isolated Perfused Rat Liver
WALTER REED ARMY INST OF RESEARCH WASHINGTON DC
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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.