Intrapulmonary Administration of Peptide Drugs In a Unique Rat Model: Increased Drug Absorption and Avoidance of "First Pass" Liver Clearance
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Authors
Hoover, Jennifer Leigh
Issue Date
1990
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
Peptide drugs represent an important therapeutic
pharmaceutical class for the treatment of many chronic illnesses.
Unfortunately, oral administration, the most favored delivery route,
often results in extremely low absorption due to degradation in the
gastrointestinal (GI) tract and frequent "first pass" liver clearance.
The low bioavailability and biological activity, following oral
administration, makes this route less than optimal for the delivery of
peptide drugs. Therefore the intrapulmonary route was investigated.
Synthetic model peptides, which varied systematically in
molecular mass, hydrogen bond number, and lipophilicity were
administered into the lungs to determine the factors which affect
intrapulmonary absorption. The results suggest that the major
determinant of gut absorption, hydrogen bond number, plays no
significant role in absorption from the lung.
Additional intrapulmonary administration studies were
performed with two potential drug candidates, U77436, a renIn
inhibitor and U75875, an HIV protease inhibitor. Each peptide
exhibited "sustained release" over ten hours.
All peptides exhibited greater than 50% absorption, suggesting
that the intrapulmonary route is a promising alternative to oral
peptide delivery.
Description
XIII, 128 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.