The Intrapulmonary, Multiple Dose Delivery of the Peptide U-71,038, A Dual Renin and HIV-Portease Inhibitor
Sheehy, Ann M.
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The oral ingestion of peptidic compounds as therapeutics is problematic due to the peptidase activity encountered in the gut, poor absorption from the intestine and rapid first-pass liver clearance. The intrapulmonary route of drug delivery offers several advantages over this traditional method: the lungs provide a vast surface area, maximized for absorption, and allow direct access to the systemic circulation. More importantly, absorption across the respiratory membrane avoids both peptidase degradation and firstpass liver clearance. The intrapulmonary route of the rat was accessed by the aerosolization of test peptides and drug deposition was achieved via an inserted trachea tube. Analysis of the drug levels in the blood was accomplished by drawing samples from a jugular vein cannula and subjecting the collections to radioimmunoassay techniques. Dose response curves and multiple dose administration data suggested that transport from the lung was a saturable phenomena, creating a "sustained release" delivery into the circulation. This pattern of steady infusion has possible clinical applications, specifically in the treatment of AIDS and hypertension.