Physiologically-Based Pharmacokinetic Model of Morphine and Morphine-3-Glucuronide in Nonalcoholic Steatohepatitis.

ABSTRACT: Nonalcoholic steatohepatitis (NASH), the progressive form of nonalcoholic fatty liver disease, is increasing in prevalence. NASH-related alterations in hepatic protein expression (e.g., transporters) and in overall physiology may affect drug exposure by altering drug disposition and elimination. The aim of this study was to build a physiologically-based pharmacokinetic (PBPK) model to predict drug exposure in NASH by incorporating NASH-related changes in hepatic transporters. Morphine and morphine-3-glucuronide (M3G) were used as model compounds. A PBPK model of morphine with permeability-limited hepatic disposition was extended to include M3G disposition and enterohepatic recycling (EHR). The model captured the area under the plasma concentration-time curve (AUC) of morphine and M3G after

SUBMITTER: Sjostedt N 

PROVIDER: S-EPMC7902445 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature