Metabolism of ethyl loflazepate in the rat, the dog, the baboon and in man
Davi, H.; Guyonnet, J.; Sales, Y.; Cautreels, W.
Arzneimittel-Forschung 35(7): 1061-1065
1985
ISSN/ISBN: 0004-4172 PMID: 2864933 Document Number: 264391
The metabolism of ethyl loflazepate (Victan), a new benzodiazepine used as an anxiolytic drug, was studied in man and several animal species. The urinary metabolites were determined and quantified following oral administration of the 14C-labeled drug. Further analysis of blood samples was carried out in order to get information on the circulating metabolites in man. Except the rat, from which only 25% of the administered dose were excreted via the kidneys, the urine appeared to be the main excretion route in man (63%) and the other animal species (80%). The major urinary metabolites were identified as being loflazepate, 3-hydroxyloflazepate, 3-hydroxydescarbethoxyloflazepate, 4'-hydroxydescarbethoxyloflazepate and 6-chloro-4-(2'-fluorophenyl)-2(1H)-quinazolinone. The observed differences on the excretion patterns between the species resulted from the presence of a large number of quantitatively minor metabolites. Analysis of human blood samples indicated that the radioactivity was almost entirely in the plasma. The main circulating metabolites were detected as descarbethoxyloflazepate, loflazepate, and 3-hydroxydescarbethoxyloflazepate.