Physiological disposition and metabolism of N-t-butylarterenol and its di-p-toluate ester (bitolterol) in the rat.

The metabolism and disposition of the bronchodilator, N-t-butylarterenol (tBA) and its di-p-toluate ester (bitolterol) were compared in the rat. Radioactivity was preferentially retained in lungs of rats compared with heart and blood after iv medication with tritium-labeled bitolterol, but was not retained in tissues after iv medication with [3H]tBA. After oral and iv medication with [3H]bitolterol, fecal radioactivity accounted for 24% of the dose and 65 and 79% of the radioactivity, respectively, was excreted in urine (0-72 hr). In comparison, urine radioactivity after oral and iv medication with [3H]tBA was 43 and 83% of the dose, respectively, and fecal radioactivity accounted for 43 or 23% of the dose, respectively (0-72 hr). Bitolterol was hydrolyzed in vitro to tBA by esterases found in various tissues including small intestine, liver, and plasma. Moreover, tBA was a substrate for catecholamine O-methyltransferase but not for monoamine oxidase. Similar metabolites were observed in urine samples of rats given either [3H]tBA or [3H]bitolterol. Urine metabolites were identified as free and conjugated forms of both tBA and 3-O-methyl-tBA.