Prodrug approaches to improving the oral absorption of antiviral nucleotide analogues.
Nucleotide analogues have been well accepted as therapeutic agents active against a number of viruses. However, their use as antiviral agents is limited by the need for phosphorylation by endogenous enzymes, and if the analogue is orally administered, by low bioavailability due to the presence of an ionizable diacid group. To circumvent these limitations, a number of prodrug approaches have been proposed. The ideal prodrug achieves delivery of a parent drug by attachment of a non-toxic moiety that is stable during transport and delivery, but is readily cleaved to release the parent drug once at the target. Here, a brief overview of several promising prodrug strategies currently under development is given.
Peterson
Larryn W
LW
University of Southern California, Department of Chemistry, Los Angeles, CA 90089-0744, USA. mckenna@usc.edu
McKenna
Charles E
CE
D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D009711:Nucleotides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010766:Phosphorylation; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014777:Virus Diseases / Q000188:drug therapy
D000998:Antiviral Agents; D009711:Nucleotides; D011355:Prodrugs