Isolated perfused rabbit lung as a model for intravascular and intrabronchial administration of bronchodilator drugs II:Isoproterenol prodrugs.
The pulmonary disposition of two diester prodrugs of isoproterenol (di-p-toluoylisoproterenol and dipivaloylisoproterenol) was studied in the isolated perfused rabbit lung preparation. High-pressure liquid chromatographic methods were developed to measure diester, monoester, isoproterenol, and 3-O-methylisoproterenol from a single 1-ml perfusate sample. The prodrugs were administered directly into the circulating perfusion medium and by endotracheal instillation. Perfusate concentrations of diester, monoester, isoproterenol, and 3-O-methylisoproterenol were measured for 180 min. The diesters were rapidly eliminated from the perfusate with a subsequent increase in monoester concentrations. Isoproterenol levels were observed within minutes of prodrug administration, peaked at 60-80 min, and declined slowly thereafter. The prodrugs were rapidly absorbed following endotracheal administration with 30-50% of the diester being metabolized during the first pass through the lung.
D000818:Animals; D001980:Bronchi; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D007442:Intubation, Intratracheal; D007545:Isoproterenol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood; D008168:Lung / Q000098:blood supply / Q000378:metabolism*; D008954:Models, Biological; D010477:Perfusion; D011817:Rabbits
C036414:di-4-toluoylisoproterenol; C015174:dipivaloylisoproterenol; D007545:Isoproterenol