Prodrugs pp 1151-1161 | Cite as

Case Study: Adefovir Dipivoxil: An Oral Prodrug of Adefovir

  • Maria Fardis
  • Reza Oliyai
Part of the Biotechnology: Pharmaceutical Aspects book series (PHARMASP, volume V)


The potential antiviral effect of adefovir (Scheme I), an acyclic nucleoside phosphonate analog of 2′-deoxyadenosine monophosphate, was first studied by Holý and De Clercq over 15 years ago (De Clercq et al., 1986, 1987; Holý et al., 1999, 2002). In this class of compounds, the ribose phosphate group is replaced with the isopolar phosphonomethyl ether functionality. Adefovir is recognized by host kinases and is phosphorylated in situ to the virologically active adefovir diphosphate (Qaqish et al., 2003). Adefovir diphosphate inhibits hepatitis B virus (HBV) DNA polymerase (reverse transcriptase) in addition to other viral DNA polymerases. This inhibition results in DNA chain termination and impairment of viral replication. The inhibition constant (Ki) for adefovir diphosphate binding to HBV DNA polymerase is 0.1 µM, while the Kis for binding to human DNA polymerases α and γ are 1.18 µM and 0.97 µM, respectively (Hepsera Package Insert 2002). Therefore, adefovir dipivoxil has a sufficient therapeutic index for clinical utility.


Adefovir Dipivoxil Pivalic Acid Oral Prodrug Diethyl Phosphonate Adefovir Diphosphate 
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Copyright information

© American Association of Pharmaceutical Scientists 2007

Authors and Affiliations

  • Maria Fardis
    • 1
  • Reza Oliyai
    • 1
  1. 1.Gilead Sciences Inc.Foster CityUSA

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