Pharmacokinetic Imaging Using ^99mTc-Mebrofenin to Untangle the Pattern of Hepatocyte Transporter Disruptions Induced by Endotoxemia in Rats.

ABSTRACT: Endotoxemia-induced inflammation may impact the activity of hepatocyte transporters, which control the hepatobiliary elimination of drugs and bile acids. ^99mTc-mebrofenin is a non-metabolized substrate of transporters expressed at the different poles of hepatocytes. ^99mTc-mebrofenin imaging was performed in rats after the injection of lipopolysaccharide (LPS). Changes in transporter expression were assessed using quantitative polymerase chain reaction of resected liver samples. Moreover, the particular impact of pharmacokinetic drug-drug interactions in the context of endotoxemia was investigated using rifampicin (40 mg/kg), a potent inhibitor of hepatocyte transporters. LPS increased ^99mTc-mebrofenin exposure in the liver (1.7 ± 0.4-fold). Kinetic modeling

SUBMITTER: Marie S 

PROVIDER: S-EPMC9028474 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature