Transcellular stomach absorption of a derivatized glucagon-like peptide-1 receptor agonist
| العنوان: | Transcellular stomach absorption of a derivatized glucagon-like peptide-1 receptor agonist |
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| المؤلفون: | Kim G. Madsen, Flemming L. Søndergaard, Jonas Ahnfelt-Rønne, Andrew J. Benie, Simon Bjerregaard, Jeanett Borregaard, Tine A. Bækdal, Betty Lomstein Pedersen, Susanne Schéele, Charles Pyke, Marie-Louise Hartoft-Nielsen, Stephen T. Buckley, Tomas Alanentalo, Rikke Bjerring Skyggebjerg, Rikke Kaae Kirk, Lotte Bjerre Knudsen, Stine J. Maarbjerg, Holger M. Strauss, Andreas Vegge, Csaba Fekete, Erzsébet Farkas, Per-Olof Wahlund |
| المصدر: | Science Translational Medicine. 10 |
| بيانات النشر: | American Association for the Advancement of Science (AAAS), 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Adult, Male, Absorption (pharmacology), Time Factors, Adolescent, Glucagon-Like Peptides, Administration, Oral, 02 engineering and technology, Pharmacology, 030226 pharmacology & pharmacy, Glucagon-Like Peptide-1 Receptor, Intestinal absorption, Young Adult, 03 medical and health sciences, Dogs, 0302 clinical medicine, Glucagon-Like Peptide 1, Oral administration, Animals, Humans, Transcellular, Glucagon-like peptide 1 receptor, Aged, Tight junction, Chemistry, Semaglutide, Cell Membrane, Stomach, Proteolytic enzymes, Epithelial Cells, General Medicine, Hydrogen-Ion Concentration, Middle Aged, 021001 nanoscience & nanotechnology, Rats, Intestinal Absorption, Gastric Mucosa, 0210 nano-technology |
| الوصف: | Oral administration of therapeutic peptides is hindered by poor absorption across the gastrointestinal barrier and extensive degradation by proteolytic enzymes. Here, we investigated the absorption of orally delivered semaglutide, a glucagon-like peptide-1 analog, coformulated with the absorption enhancer sodium N-[8-(2-hydroxybenzoyl) aminocaprylate] (SNAC) in a tablet. In contrast to intestinal absorption usually seen with small molecules, clinical and preclinical dog studies revealed that absorption of semaglutide takes place in the stomach, is confined to an area in close proximity to the tablet surface, and requires coformulation with SNAC. SNAC protects against enzymatic degradation via local buffering actions and only transiently enhances absorption. The mechanism of absorption is shown to be compound specific, transcellular, and without any evidence of effect on tight junctions. These data have implications for understanding how highly efficacious and specific therapeutic peptides could be transformed from injectable to tablet-based oral therapies. |
| تدمد: | 1946-6242 1946-6234 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::da23aec5d09c52d95e43b0ca9e999cdbTest https://doi.org/10.1126/scitranslmed.aar7047Test |
| رقم الانضمام: | edsair.doi.dedup.....da23aec5d09c52d95e43b0ca9e999cdb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19466242 19466234 |
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