Uptake and biotransformation of ibuterol and terbutaline in isolated perfused rat and guinea pig lungs

The lung uptake and biotransformation of [³H]terbutaline and [³H]ibuterol (diisobutyrate ester of terbutaline) was studied using isolated perfused and ventilated rat and guinea pig lungs. The lung extraction ratio, as calculated from the concentration of drug in the inflowing and outflowing medium, in single pass studies of ibuterol ranged from 0.32 to 0.41 at inflowing concentrations 1 × 10^?5 and 1 × 10^?7M and that of terbutaline ranged from 0.013 to 0.021. Ibuterol was hydrolyzed to terbutaline but no further biotransformation of terbutaline was found. The lung clearance of ibuterol (1 × 10^?7M) was estimated to 0.092 ml/sec. When ibuterol (1 × 10^?7M) was infused together with eserine, an esterase inhibitor, the clearance of ibuterol decreased to 0.088 ml/sec (eserine 1 × 10^?5M) and 0.045 ml/sec (eserine 1 × 10^?4M). The latter value was significantly lower (P < 0.001) than control.