Shargel L, Dorrbecker S A, Levitt M
Drug Metab Dispos. 1976 Jan-Feb;4(1):65-71.
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.
在大鼠体内比较了支气管扩张剂N-叔丁基肾上腺素（tBA）及其二对甲苯酸酯（双甲苯喘定）的代谢与处置情况。静脉注射氚标记的双甲苯喘定后，与心脏和血液相比，放射性优先保留在大鼠肺中，但静脉注射[3H]tBA后，放射性未保留在组织中。口服和静脉注射[3H]双甲苯喘定后，粪便放射性分别占给药剂量的24%，尿液中分别排出给药剂量的65%和79%的放射性（0 - 72小时）。相比之下，口服和静脉注射[3H]tBA后，尿液放射性分别占给药剂量的43%和83%，粪便放射性分别占给药剂量的43%或23%（0 - 72小时）。双甲苯喘定在体外可被包括小肠、肝脏和血浆在内的各种组织中的酯酶水解为tBA。此外，tBA是儿茶酚-O-甲基转移酶的底物，但不是单胺氧化酶的底物。给大鼠注射[3H]tBA或[3H]双甲苯喘定后，在尿液样本中观察到相似的代谢产物。尿液代谢产物被鉴定为tBA和3-O-甲基-tBA的游离形式和结合形式。
