2021 journal article

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

PLOS ONE, 16(4).

By: H. Enomoto n, J. Yeatts n, L. Carbajal n, B. Krishnan, J. Madan, S. Laumas, A. Blikslager n, K. Messenger n

co-author countries: United States of America 🇺🇸
MeSH headings : Administration, Oral; Animals; Celiac Disease / drug therapy; Drug Liberation; Duodenum / metabolism; Jejunum / metabolism; Oligopeptides / administration & dosage; Oligopeptides / pharmacokinetics; Oligopeptides / therapeutic use; Swine
Source: Web Of Science
Added: May 17, 2021

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.