Integration of Gut Microbiome Metabolism in a PBBM-PBPK Model: its impact on the Sulfasalazine absorption

Authors: Plait F, Amaral Silva D, Zhou H, Fotaki N, Pereira GG, Lukacova V
Conference: AAPS
Keywords: AAPS2024, gastrointestinal (GI) tract., gastroplus, pbbm, PBPK
Software: GastroPlus®
Division: PBPK

Purpose

  • Inflammatory bowel disease (IBD) is a recurrent or continuous inflammation of the bowel that affects 1.4 million patients in the United States.
  • The two main forms of IBD are Crohn’s disease and ulcerative colitis.
  • IBD’s first in-line treatments are sulfasalazine and its metabolite 5-aminosalicylic acid (5-ASA, also called mesalamine). 5-ASA is produced by the gut microbiome present in the colon lumen (Figure 1).
  • Development of generic drug products for IBD is based on pharmacodynamic endpoint studies as the local concentration at the site of action cannot be sampled in humans and may not be reflected in plasma exposure.
  • Physiologically based pharmacokinetic (PBPK) models can provide insight into drug partitioning into the gut wall.
  • PBPK may support the development and regulatory assessment of GI locally acting new and generic drug products.

By Fiona Plait, Daniela Silva, Haiying Zhou, Nikoletta Fotaki, Gabriela Garrastazu Pereira, Viera Lukacova

American Association of Pharmaceutical Scientists (AAPS) PharmSci 360, October 20-23, 2024, Salt Lake City, Utah