Uptake of propranolol by the lung and its displacement by other drugs: involvement of the alveolar macrophage.
The role of the alveolar macrophage in the uptake of 3H-propranolol by the isolated perfused rabbit lung and displacement of 3H-propranolol from this site has been investigated. Removal of 3H-propranolol (100 microgram) by the lung was characterized by a rapid distribution phase (t1/2 min) and a slower elimination phase with a clearance of 22.4 ml/min (t1/2 = 47 min). Addition of chlorpromazine (1 mg) at 30 min was followed by a twofold increase in perfusate concentrations of 3H-propranolol which was also associated with a reduction of 3H-propranolol in macrophages recovered from lungs at the end of perfusion experiments. Experiments using isolated alveolar macrophages demonstrated uptake of propranolol and marked inhibition by 100-fold higher concentrations of chlorpromazine and imipramine. In the intact dog, injection of imipramine (1 mg/kg) 60-70 min after bolus injection of 3H-propranolol (0.3 mg/kg) was associated with an immediate increase in blood levels of 3H-propranolol consistent with tissue redistribution. It is concluded that chlorpromazine and imipramine can displace propranolol from the lung,and that the alveolar macrophage is involved in this process.
D000818:Animals; D002746:Chlorpromazine / Q000494:pharmacology; D004285:Dogs; D004347:Drug Interactions; D006439:Hemodynamics / Q000187:drug effects; D007099:Imipramine / Q000494:pharmacology; D008168:Lung / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D010477:Perfusion; D011433:Propranolol / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000378:metabolism; D011817:Rabbits; D014018:Tissue Distribution
D011433:Propranolol; D007099:Imipramine; D002746:Chlorpromazine