Nonalcoholic steatohepatitis increases plasma retention of sorafenib-glucuronide in a mouse model by altering hepatocyte hopping.

ABSTRACT: Hepatocyte hopping is the hepatocyte-to-sinusoid-to-hepatocyte shuttling that increases the efficiency of hepatic elimination of xenobiotics. This phenomenon is mediated via efflux of hepatic metabolites by Mrp3 and reuptake by Oatp transporters in sequential hepatocytes until eventual biliary efflux by Mrp2. Sorafenib-glucuronide (SFB-G), the major metabolite of sorafenib (SFB), undergoes hepatocyte hopping, leading to efficient biliary elimination. Nonalcoholic steatohepatitis (NASH) alters the functioning of transporters involved in hepatocyte hopping. The purpose of this study was to quantify the effect of NASH on the three drug disposition processes of hepatocyte hopping. Male FVB and C57BL/6 wild-type (WT), Oatp1a/1b cluster knockout (O^-/-), and Mrp2 knockout

SUBMITTER: Toth E 

PROVIDER: S-EPMC11628858 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature