In vivo assessment of a delayed release formulation of larazotide acetate indicated for celiac disease using a porcine model

Autor:	Sandeep Laumas, James L. Yeatts, Hiroko Enomoto, Liliana Carbajal, Anthony T. Blikslager, Jay Madan, B Radha Krishnan, Kristen M. Messenger
Jazyk:	angličtina
Rok vydání:	2021
Předmět:	Swine Administration Oral Pharmacology Jejunum Pig Models Medicine and Health Sciences Mammals Gastrointestinal tract Multidisciplinary Pharmaceutics Chemistry digestive oral and skin physiology Eukaryota Animal Models medicine.anatomical_structure Experimental Organism Systems Vertebrates Small Intestine Medicine Anatomy Oligopeptides Research Article Drug Administration Duodenum Science Research and Analysis Methods digestive system Drug Therapy Larazotide Pharmacokinetics In vivo medicine Animals Dosing Organisms Biology and Life Sciences Small intestine Gastrointestinal Tract Celiac Disease Drug Liberation Amniotes Animal Studies Digestive System Zoology
Zdroj:	PLoS ONE, Vol 16, Iss 4, p e0249179 (2021) PLoS ONE
ISSN:	1932-6203
Popis:	There is no FDA approved therapy for the treatment of celiac disease (CeD), aside from avoidance of dietary gluten. Larazotide acetate (LA) is a first in class oral peptide developed as a tight junction regulator, which is a lead candidate for management of CeD. A delayed release formulation was tested in vitro and predicted release in the mid duodenum and jejunum, the target site of CeD. The aim of this study was to follow the concentration versus time profile of orally administered LA in the small intestine using a porcine model. A sensitive liquid chromatography/tandem mass spectrometry method was developed to quantify LA concentrations in porcine intestinal fluid samples. Oral dosing of LA (1 mg total) in overnight fasted pigs resulted in time dependent appearance of LA in the distal duodenum and proximal jejunum. Peak LA concentrations (0.32–1.76 μM) occurred at 1 hour in the duodenum and in proximal jejunum following oral dosing, with the continued presence of LA (0.02–0.47 μM) in the distal duodenum and in proximal jejunum (0.00–0.43 μM) from 2 to 4 hours following oral dosing. The data shows that LA is available in detectable concentrations at the site of CeD.
Databáze:	OpenAIRE
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