Desolvation Energy: The Major Determinate of Absorption in a Model Peptide Series
Karls, Michael S.
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The delivery of tetrapeptidic and higher oligopeptidic drugs is problematic due to degradation of the peptides in the gastrointestinal tract and low absorption through the intestinal mucosa. To address the absorption problem, these studies utilized two series of digestion-resistant peptides to determine whether molecular weight, lipophilicity, or the number of theoretical hydrogen bonding sites most influenced absorption. In previous in vitro human colon adenocarcinomona cell and in situ rabbit perfusion model system studies, absorption of these peptides was found to be most influenced by the number of hydrogen bonding sites. This paper describes in vivo rat studies which were undertaken to supplement these earlier studies. The results support the earlier findings that the predominant factor influencing absorption for these peptides is the number of theoretical hydrogen bonding sites, the major determinant of desolvation energy. Molecular weight also plays a secondary role in the this absorption.