Changes in absorptive capacity and first‐pass metabolism in the small intestine affect oral
drug bioavailability. Characterization of such changes as a consequence of inflammation is
important for developing physiologically‐based pharmacokinetic (PBPK) models for
inflammatory bowel disease. We sought to elucidate the impact of small intestinal Crohn's
disease (CD) on villous length and CYP3A4 expression in children. Freshly frozen duodenal
and terminal ileum (TI) biopsies from 107 children (1–19 years) with and without CD were …

Background: Villi play a critical role in making the small intestine the major site of absorption
for orally administered drugs. Active small intestinal inflammation in Crohn's disease (CD) is
associated with histopathological changes to the absorptive epithelium such as villous
blunting. The structural pathologies frequently observed in active CD have the potential to
alter oral drug bioavailability. Cytochrome P450 3A4 (CYP3A4) is the most abundant
cytochrome P450 isoform in the small intestine and is capable of extensively metabolizing …