The Physiological Disposition of Ibuterol, Terbutaline and Isoproterenol after Endotracheal Instillation to Rats

Abstract

1. The absorption from the respiratory tract and biotransformation of three bronchodilating drugs, terbutaline, ibuterol (diisobutyrate ester of terbutaline) and isoproterenol, have been studied in rats after endotracheal instillation.

2. At 2-15 min after dosage, ibuterol is more rapidly absorbed from the respiratory tract than terbutaline, but later (15-35 min), absorption of ibuterol is about the same as terbutaline. Absorption of isoproterenol is rapid throughout the experiment. Absorption rates have been related to the physical-chemical properties of the compounds.

3. No significant biotransformation of terbutaline was noted in the rat lung at any time after dosage, but ibuterol is extensively hydrolysed to terbutaline. Extensive biotransformation of isoproterenol to 3-methoxy-isoproterenol and an unidentified metabolite occurred. Metabolites of terbutaline and isoproterenol were found in serum and liver.