Adefovir

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Adefovir
Adefovir2DCSD.svg
Systematic (IUPAC) name
{[2-(6-amino-9H-purin-9-yl)ethoxy]methyl}phosphonic acid
Clinical data
Trade names Hepsera
AHFS/Drugs.com monograph
Pregnancy cat. B3 (AU) C (US)
Legal status Prescription Only (S4) (AU) -only (CA) POM (UK) -only (US)
Routes Oral
Pharmacokinetic data
Bioavailability 59%
Protein binding <4%
Half-life 7.5 hours
Excretion Urine
Identifiers
CAS number 106941-25-7 N
ATC code J05AF08
PubChem CID 60172
DrugBank DB00718
ChemSpider 54252 YesY
UNII 6GQP90I798 YesY
KEGG D02768 YesY
ChEMBL CHEMBL484 YesY
NIAID ChemDB 028595
Chemical data
Formula C8H12N5O4P 
Mol. mass 273.186 g/mol
 N (what is this?)  (verify)

Adefovir is a prescription medicine used to treat (chronic) infections with hepatitis B virus. Adefovir was previously called bis-POM PMEA, with trade names Preveon and Hepsera. It is an orally-administered nucleotide analog reverse transcriptase inhibitor (ntRTI). It can be formulated as the pivoxil prodrug adefovir dipivoxil.

Uses[edit]

It is used for treatment of hepatitis B [1][2] and herpes simplex virus infection. [3]

It is a failed treatment for HIV.[3][4]

History[edit]

Adefovir was invented in the Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic by Antonín Holý, and the drug was developed by Gilead Sciences for HIV with the brand name Preveon. However, in November 1999, an expert panel advised the U.S. Food and Drug Administration (FDA) not to approve the drug due to concerns about the severity and frequency of kidney toxicity when dosed at 60 or 120 mg. The FDA followed that advice, refusing to approve adefovir as a treatment for HIV.

Gilead Sciences discontinued its development for HIV treatment in December 1999 but continued to develop the drug for hepatitis B (HBV), where it is effective with a much lower dose of 10 mg. FDA approval for use in the treatment of hepatitis B was granted on September 20, 2002, and adefovir is sold for this indication under the brand name Hepsera.

Adefovir became an approved treatment for HBV in the United States in September 2002 and in the European Union in March 2003.

Mechanism of action[edit]

Adefovir dipivoxil

Adefovir works by blocking reverse transcriptase, an enzyme that is crucial for the hepatitis B virus (HBV) to reproduce in the body.

It is approved for the treatment of chronic hepatitis B in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (primarily ALT) or histologically active disease.

The main benefit of adefovir over lamivudine (the first NRTI approved for the treatment of hepatitis B) is that it takes a much longer period of time before the virus develops resistance to it.

Adefovir dipivoxil contains two pivaloyloxymethyl units, making it a prodrug form of adefovir.

References[edit]

  1. ^ Marcellin P, Chang TT, Lim SG et al. (February 2003). "Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B". N. Engl. J. Med. 348 (9): 808–16. doi:10.1056/NEJMoa020681. PMID 12606735. 
  2. ^ Manolakopoulos S, Bethanis S, Koutsounas S et al. (February 2008). "Long-term therapy with adefovir dipivoxil in hepatitis B e antigen-negative patients developing resistance to lamivudine". Aliment. Pharmacol. Ther. 27 (3): 266–73. doi:10.1111/j.1365-2036.2007.03567.x. PMID 17988233. 
  3. ^ a b ADHOC International Steering Committee (October 2002). "A randomized placebo-controlled trial of adefovir dipivoxil in advanced HIV infection: the ADHOC trial". HIV Med. 3 (4): 229–38. doi:10.1046/j.1468-1293.2002.00111.x. PMID 12444940. 
  4. ^ Fisher EJ, Chaloner K, Cohn DL et al. (September 2001). "The safety and efficacy of adefovir dipivoxil in patients with advanced HIV disease: a randomized, placebo-controlled trial". AIDS 15 (13): 1695–700. doi:10.1097/00002030-200109070-00013. PMID 11546945. 

External links[edit]