The Intrapulmonary, Multiple Dose Delivery of the Peptide U-71,038, A Dual Renin and HIV-Portease Inhibitor
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Authors
Sheehy, Ann M.
Issue Date
1991
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
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.
Description
vi, 41 p.
Citation
Publisher
Kalamazoo College
License
U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.