Disposition and metabolism of formoterol fumarate, a new bronchodilator, in rats and dogs.

1. The disposition and metabolism of formoterol fumarate, a highly potent beta 2-adrenoceptor stimulant, were studied in rats and dogs. 2. After oral administration of [3H] formoterol fumarate to dogs, unchanged formoterol accounted for greater than 60% of the plasma radioactivity immediately after dosage; greater than 20% was due to the unchanged drug until 12 h after dosage. In contrast, only 1-3% of the radioactivity was present as unchanged drug in rat plasma. After i.v. dosage, unchanged drug was much higher in both species. The elimination half-life of formoterol was 4-6 h in dogs and 1.7 h in rats. 3. In both species, 36-45% of the dose was excreted in urine and 50-56% in faeces in 72 h, irrespective of the administration route. Biliary excretion after oral dosage amounted to 65 and 31% in rats and dogs, respectively. 4. T.l.c. before and after enzymic hydrolysis revealed that the drug was excreted in urine and bile of rats mostly as a conjugate. Dog urine also contained the conjugate but the unchanged drug was much higher than in rats. The conjugated metabolite was purified from rat urine and identified as the 2-O-glucuronide. The glucuronide was the only metabolite detected in the urine and bile of rats and in the urine of dogs.