Pulmonary penetration of alpha 1-proteinase inhibitor administered parenterally to dogs.
To study the penetration of alpha 1-proteinase inhibitor (A1Pl) into the lungs of healthy dogs, 83 mg/kg of active A1Pl was administered intravenously over 30 min followed by a bolus of 131I-A1Pl. Animals were lavaged 2 to 72 h after infusion, sequential gamma camera scans were acquired, and urine was analyzed for the excretion of desmosine. After a distribution phase, infused A1Pl left the bloodstream with a half-life of 103 +/- 24 h. Analysis of plasma antiprotease activity demonstrated preservation of function of the infused A1Pl. Lavage fluid A1Pl concentration and activity were significantly increased 24 h after infusion. Gamma camera scans demonstrated that lung, liver, and spleen acquired 131I-A1Pl similarly; radioactivities per gram of tissue of these organs were similar at autopsy. Excretion of desmosine did not decrease from a baseline of 157 +/- 59 nmol/24 h after A1Pl infusion, indicating no effect of A1Pl infusion on background elastolysis. These data suggest that intravenous administration of A1Pl can raise lung antiproteinase levels within 24 h despite the absence of preferential uptake by the lung of the infused protein.
D000818:Animals; D001798:Blood Proteins / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D001992:Bronchoalveolar Lavage Fluid / Q000032:analysis / Q000378:metabolism; D003895:Desmosine / Q000652:urine; D004285:Dogs; D006207:Half-Life; D007262:Infusions, Intravenous; D007457:Iodine Radioisotopes; D008168:Lung / Q000378:metabolism*; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D013997:Time Factors; D014018:Tissue Distribution; D014915:Whole-Body Counting; D000515:alpha 1-Antitrypsin
D001798:Blood Proteins; D007457:Iodine Radioisotopes; D011480:Protease Inhibitors; D000515:alpha 1-Antitrypsin; D003895:Desmosine; D010196:Pancreatic Elastase