High capacity for pulmonary first-pass elimination of propranolol in rats

Plasma propranolol concentrations after i.v. and i.a. 1, 2.5, 5 and 10 mg kg-1 doses of the drug given intravenously or intra-arterially have been compared in 7-week-old male Wistar rats. The areas under the curves after i.a. dosing were almost twice those after i.v. dosing at any dose, despite the elimination half-lives being the same. The difference in total body clearance after i.a. dosing from that after i.v. dosing indicated a significant contribution by pulmonary clearance, which ranged from about 20 to 30 mL min-1 kg-1, to the overall first-pass elimination after the i.v. administration. The pulmonary extraction ratio was approximately 0.4 to 0.5 at the i.v. doses used. Mean pulmonary transit time was estimated to be about 1 to 2 min. There was no dose-dependence in the pulmonary first-pass elimination kinetics of propranolol.