Physiologically Based Biopharmaceutics Model (PBBM) of Minimally Absorbed Locally Acting Drugs in the Gastrointestinal Tract-Case Study: Tenapanor.

ABSTRACT: A physiologically based biopharmaceutics model (PBBM) was developed to predict stool and urine sodium content in response to tenapanor administration in healthy subjects. Tenapanor is a minimally absorbed small molecule that inhibits the sodium/hydrogen isoform 3 exchanger (NHE3). It is used to treat irritable bowel syndrome with constipation (IBS-C). Its mode of action in the gastrointestinal tract reduces the uptake of sodium, resulting in an increase in water secretion in the intestinal lumen and accelerating intestinal transit time. The strategy employed was to perform drug-drug interaction (DDI) modelling between sodium and tenapanor, with sodium as the "victim" administered as part of daily food intake and tenapanor as the "perpetrator" altering sodium absorption. Food effect was mod

SUBMITTER: Stamatopoulos K 

PROVIDER: S-EPMC10747343 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature