PT  - JOURNAL ARTICLE
AU  - J. V. MU
AU  - Z. H. ISRAILI
AU  - P. G. DAYTON
TI  - STUDIES OF THE DISPOSITION AND METABOLISM OF MEFLOQUINE HCI ( WR 142,490), A QUINOLINEMETHANOL ANTIMALARIAL, IN THE RAT Limited Studies with an Analog, WR 30,090
DP  - 1975 May 01
TA  - Drug Metabolism and Disposition
PG  - 198--210
VI  - 3
IP  - 3
4099  - http://dmd.aspetjournals.org/content/3/3/198.short
4100  - http://dmd.aspetjournals.org/content/3/3/198.full
SO  - Drug Metab Dispos1975 May 01; 3
AB  - The overall fate of the quinolinemethanol antimalarial. mefloquine-HCI IWR 142.490. erythro-DL-α-( 2-piperidyl)-2.8-bis( trifluoromethyl)-4-quinolinemethanol hydrochloridej was investigated in the rat with 14C-labeled drug. Despite its extensive binding to plasma proteins. high tissue/ plasma concentration ratios were found. Fecal excretion accounted for most of the drug and metabolites. This fate was rationalized on the basis of physical properties of mefloquine ( and its metabolites) and extensive biliary and gastric secretion. followed by reabsorption. Evidence was obtained for the formation of several metabolites. Limited studies were carried out in rats. dogs. and one human subject with another quinolinemethanol. WR 30.090-14C [DL-6.8-dichloro-2-(3', 4'-dichlorophenyl) -α -(di - n - butylaminomethyl) - 4 - quinolinemethanol hydrochloridel. Its general fate and physical properties were similar to mefloquine. The disposition of the two quinoline compounds studied was compared to that of quinine and quinidine reported in the literature. This revealed that modification of the quinine molecule resulted in new drugs which were more highly bound and exhibited longer half-lives than quinine. Copyright © 1975 by The American Society for Pharmacology and Experimental Therapeutics