Tracazolate metabolites in rat tissue

FR Zuleski, KM Kirkland, MD Melgar and JO Malbica

Tracazolate (4-n-butylamino-1-ethyl-6-methyl-1H-pyrazolo[3,4-b] pyridine-5-carboxylic acid ethyl ester) undergoes extensive biotransformation to lipophilic metabolites following oral dosage to male rats. Twenty-one metabolites were identified in a plasma hexane extract by mass spectrometry. Coadministration of unlabeled tracazolate with its stable carbon-13 isotope expedited the isolation and identification of 11 biotransformation products. The various metabolites resulted from either hydrolysis, oxidation, dealkylation, or conversion of an ethyl group to a vinyl group and also from combinations of these biotransformation reactions. Brain extract contained tracazolate and 12 of the metabolites found in plasma. Extracts of fat contained tracazolate and nine of the plasma metabolites. An uncommon type of metabolite less polar than tracazolate (1-vinyl tracazolate) was isolated by HPLC and identified by mass spectrometry.

Volume 13, Issue 2, pp. 139-147, 03/01/1985
Copyright © 1985 by American Society for Pharmacology and Experimental Therapeutics