Related Experiment Video
Updated: Aug 15, 2026

A Competent Hepatocyte Model Examining Hepatitis B Virus Entry through Sodium Taurocholate Cotransporting Polypeptide as a Therapeutic Target
Published on: May 10, 2022
Liver targeting of hepatitis-B antiviral lamivudine using the HepDirect prodrug technology
K Raja Reddy1, Timothy J Colby, James M Fujitaki
1Department of Chemistry, Metabasis Therapeutics, Inc., 9390 Towne Centre Drive, Building 300, San Diego, CA 92121, USA.
Abstract:
A new class of phosphate and phosphonate prodrugs, called HepDirect prodrugs, has been developed to deliver drugs to the liver while simultaneously diminishing drug exposure to extra-hepatic tissues. The technology combines liver-selective cleavage and kinase by pass with high plasma and tissue stability to achieve increased drug levels in the liver. Lamivudine (LMV), a nucleoside analogue, is a currently approved treatment for hepatitis B infection, but shows modest efficacy and significant drug resistance due to inefficient phosphorylation. LMV is inadequately phosphorylated to the corresponding nucleoside triphosphate in rat and human hepatocytes. A HepDirect prodrug of LMV monophosphate generated 34-fold higher levels of the triphosphate in rat hepatocytes and 320-fold higher triphosphate levels in the liver of treated rats relative to LMV.
Related Concept Videos
Hepatitis
Antiviral Nucleoside Inhibitors
Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test
Effect of Hepatic Disease on Pharmacokinetics: Active Drug, Metabolite and Fraction of Metabolized Drug
Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow

