HepDirect prodrugs for targeting nucleotide-based antiviral drugs to the liver

Curr Opin Investig Drugs. 2006 Feb;7(2):109-17.

Abstract

HepDirect prodrugs represent a novel class of cytochrome P450-activated prodrugs capable of targeting certain drugs to the liver. In this review, the HepDirect prodrug concept and its use for the delivery of nucleotides to the liver for the treatment of viral hepatitis is summarized. Preclinical and clinical data for the most advanced HepDirect prodrug, pradefovir, highlight the liver-targeting capability of these prodrugs, and the potential benefit of liver targeting on drug efficacy, safety and viral resistance.

Publication types

  • Review

MeSH terms

  • Adenine / administration & dosage
  • Adenine / analogs & derivatives
  • Adenine / pharmacokinetics
  • Adenine / therapeutic use
  • Animals
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / pharmacokinetics
  • Antiviral Agents / therapeutic use
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / metabolism
  • Drug Delivery Systems*
  • Haplorhini
  • Hepatitis B / drug therapy
  • Hepatitis B / enzymology
  • Humans
  • Liver / enzymology*
  • Liver / virology
  • Nucleotides / administration & dosage*
  • Nucleotides / pharmacokinetics
  • Nucleotides / therapeutic use
  • Organophosphonates / pharmacokinetics
  • Organophosphonates / therapeutic use
  • Organophosphorus Compounds / administration & dosage
  • Organophosphorus Compounds / pharmacokinetics
  • Phosphotransferases / metabolism
  • Prodrugs / administration & dosage*
  • Prodrugs / pharmacokinetics
  • Randomized Controlled Trials as Topic
  • Rats

Substances

  • Antiviral Agents
  • Nucleotides
  • Organophosphonates
  • Organophosphorus Compounds
  • Prodrugs
  • adefovir
  • Cytochrome P-450 Enzyme System
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • Phosphotransferases
  • nucleoside phosphotransferase
  • pradefovir
  • Adenine