Use of PBBM-PBPK To Predict Mesalamine Delayed-Release Oral Drug Products Performance in Both Healthy and Disease Physiologies

Authors: Amaral Silva D, Le Merdy M, Zhou H, Fotaki N, Bu Y, AI-Ghabeish M, Ren P, Wu F
Conference: AAPS
Keywords: AAPS 2025, anti-inflammatory drug, gastroplus, oral drug delivery, pbbm, PBPK
Software: GastroPlus®

Purpose

Mesalamine (5-aminosalicylic acid (5-ASA)) is an anti-inflammatory drug indicated for the treatment of ulcerative colitis (UC) and Crohn’s disease (CD). 5-ASA acts locally in the intestines [1] and is primarily metabolized to the N-acetyl metabolite (N-Ac-5-ASA) by N-acetyltransferase 1 (NAT1) in the intestinal wall and liver. The efficacy of 5-ASA treatment can be optimized by using modified release formulations, which maximizes the local drug concentration at the site of inflammation [2]. Asacol® and Mesasal® are examples of commercially available delayed-release 5-ASA formulations. [3]. Predicting the in vivo behavior of such formulations can be challenging since many factors other than lumen pH play a role.

By Daniela Silva, Maxime Le Merdy, Haiying Zhou, Nikoletta Fotaki, Yingzi Bu, Manar AI-Ghabeish, Ping Ren, Fang Wu

American Association of Pharmaceutical Scientists (AAPS) PharmSci360, November 9-12, 2018, San Antonio, TX