METABOLISM OF IOPHENOXIC ACID IN THE DOG

¹ Departments of Medicine and of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire

The biliary and urinary metabolites of iophenoxic acid were characterized in experiments on 12 dogs by thin-layer chromography, countercurrent distribution, analysis of isolated peaks for glucuronic acid content and various hydrolysis charaeteristics. Except for one experiment, iophenoxic acid itself was not excreted in more than trace amounts. The major metabolites were a diglucuronide and the acyl and ethereal monoglucuronides. A fourth metabolite, possibly the result of side chain oxidation, has been detected but not completely characterized. -Glucuronidase hydrolysis in many samples was complete and in others incomplete, for unknown reasons. Alkaline hydrolysis of the acyl linkage was demonstrable, but the procedure itself is extremely sensitive to the concentration of alkali and hence of unpredictable value in the quantification of metabolites. The metabolites of iophenoxic acid are themselves relatively lipid soluble, although far less so than the parent compound. However, it is unlikely that their lipid sohubility per se is the major determinant of the unique persistence of iophenoxic acid; the rate of conjugate formation appears to be a more important factor.