Desolvation Energy: A Major Determinant of Absorption, But Not Clearance, of Peptides in Rats
- 1 January 1991
- journal article
- Published by Springer Science and Business Media LLC in Pharmaceutical Research
- Vol. 8 (12), 1477-1481
- https://doi.org/10.1023/a:1015882030289
Abstract
The oral delivery of peptidic drugs is problematic because of their degradation in the gastrointestinal tract and low absorption through the intestinal mucosa. Earlier in vitro studies with two series of digestion-resistant, radiolabeled peptides that varied in physical properties (molecular weight, lipophilicity, and hydrogen bonding sites) had suggested that intestinal transport of these peptides was most influenced by the number of hydrogen bonding sites, the major determinant of desolvation energy. To determine whether this correlation could be confirmed in vivo, intestinal absorption was determined by comparing the biliary and urinary recovery of these radiolabeled peptides in rats given intravenous or intraduodenal doses. Absorption was inversely correlated to the number of calculated hydrogen bonding sites for the model peptides, similar to what had been found in vitro. Clearance by liver and kidneys appeared to be unaffected by desolvation energy but was well correlated with lipophilicity.Keywords
This publication has 7 references indexed in Scilit:
- The Influence of Peptide Structure on Transport Across Caco-2 CellsPharmaceutical Research, 1991
- Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeabilityGastroenterology, 1989
- Metabolism of cyclosporine.1985
- Barrier function of epitheliaAmerican Journal of Physiology-Gastrointestinal and Liver Physiology, 1981
- Mesenteric venous blood sampling in vivo in the rat.1973
- Molecular forces governing non-electrolyte permeation through cell membranesProceedings of the Royal Society of London. B. Biological Sciences, 1969
- Chronic intravenous cannulas for ratsJournal of Applied Physiology, 1964