HepDirect prodrugs for targeting nucleotide-based antiviral drugs to the liver.
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.
Erion
Mark D
MD
Metabasis Therapeutics Inc, La Jolla, CA 92037, USA. erion@mbasis.com
Bullough
David A
DA
Lin
Chin-Chung
CC
Hong
Zhi
Z
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D016503:Drug Delivery Systems; D000882:Haplorhini; D006509:Hepatitis B / Q000188:drug therapy / Q000201:enzymology; D006801:Humans; D008099:Liver / Q000201:enzymology* / Q000821:virology; D009711:Nucleotides / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D063065:Organophosphonates / Q000493:pharmacokinetics / Q000627:therapeutic use; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics; D010770:Phosphotransferases / Q000378:metabolism; D011355:Prodrugs / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016032:Randomized Controlled Trials as Topic; D051381:Rats
D000998:Antiviral Agents; D009711:Nucleotides; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D011355:Prodrugs; C053001:adefovir; D003577:Cytochrome P-450 Enzyme System; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D010770:Phosphotransferases; C021892:nucleoside phosphotransferase; C497721:pradefovir; D000225:Adenine