Practolol and its metabolites: tissue localization and retention in the hamster

SE Rosenbaum, WE Lindup and TC Orton

The disposition of [14C]practolol and its tissue association in the male Syrian hamster were investigated after p.o. administration. After an acute dose of 400 mg/kg, there was a marked persistence in the eye of total radioactivity (primarily practolol; approximate T 1/2 = 7 days) and nonextractable radioactivity which showed minimal decay over 7 days. Nonextractable radioactivity was also found in other tissues (liver, skin, small intestine and skeletal muscle examined). The level of total and nonextractable radioactivity was linearly related to dose (800 mg/kg highest dose examined). There was a marked accumulation of total and nonextractable radioactivity in the eye (7- and 14-fold, respectively) and skin (6- and 7-fold) after daily administration of 400 mg/kg for 22 days. The association of practolol metabolites with tissue macromolecules might explain the immunological changes in patients with the practolol-induced oculomucocutaneous syndrome. The adverse effects of practolol in humans have not yet been reproduced in any laboratory species and so the results must be interpreted with caution in relation to the toxicity of compound.

Volume 234, Issue 2, pp. 485-490, 08/01/1985
Copyright © 1985 by American Society for Pharmacology and Experimental Therapeutics