The influences of the route of administration on the metabolism and excretion of bitolterol, a new bronchodilator, in the rat.

1. [3H]Bitolterol, an ester prodrug to colterol (N-t-butyl-arterenol), when administered orally, was excreted mostly in the urine; approx. equal amounts of 3H were found in urine and faeces after intraperitoneal or intravenous injection. 2. Half the dose was excreted in the bile following parenteral administration, while only a small amount of radioactivity was found in bile after oral dosage. The biliary-excreted material consisted mainly of glucuronides, for all routes of administration. 3. The glucuronides of colterol and 3-O-methyl-colterol were excreted in urine after oral administration of bitolterol. In addition to the glucuronides, free colterol and 3-O-methyl-colterol were excreted in urine following parenteral administration. 4. A part of bitolterol was hydrolysed to colterol in rat stomach, and bitolterol was more rapidly hydrolysed to colteral with homogenates of intestinal mucosa than with stomach homogenates in vitro.