A Parent-Metabolite Middle-Out PBPK Model for Genistein and Its Glucuronide Metabolite in Rats: Integrating Liver and Enteric Metabolism with Hepatobiliary and Enteroluminal Transport to Assess Glucuronide Recycling.

ABSTRACT: Background: Glucuronide recycling in the gut and liver profoundly affects the systemic and/or local exposure of drugs and their glucuronide metabolites, impacting both clinical efficacy and toxicity. This recycling also alters drug exposure in the colon, making it critical to establish local concentration for drugs targeting colon (e.g., drugs for colon cancer and inflammatory bowel disease). Methods: In this study, a parent-metabolite middle-out physiologically based pharmacokinetic (PBPK) model was built for genistein and its glucuronide metabolite to estimate the systemic and local exposure of the glucuronide and its corresponding aglycone in rats by incorporating UDP-glucuronosyltransferase (UGT)-mediated metabolism and transporter-dependent glucuronide disposition in the

SUBMITTER: Ramisetty BS 

PROVIDER: S-EPMC12300792 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature