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Adefovir

Clinical data
AHFS/Drugs.com	Monograph
Routes of administration	Oral
ATC code	J05AF08 (WHO)
Legal status
Legal status	In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability	59%
Elimination half-life	7.5 hours
Identifiers
IUPAC name {methyl}phosphonic acid
CAS Number	106941-25-7
PubChem CID	60172
DrugBank	APRD00781
ChemSpider	54252
UNII	6GQP90I798
KEGG	D02768
ChEMBL	ChEMBL484
NIAID ChemDB	028595
CompTox Dashboard (EPA)	DTXSID6046214
ECHA InfoCard	100.106.235
Chemical and physical data
Formula	C8H12N5O4P
Molar mass	273.186 g/mol g·mol
3D model (JSmol)	Interactive image
SMILES O=P(O)(O)COCCn1c2ncnc(c2nc1)N
InChI InChI=1S/C8H12N5O4P/c9-7-6-8(11-3-10-7)13(4-12-6)1-2-17-5-18(14,15)16/h3-4H,1-2,5H2,(H2,9,10,11)(H2,14,15,16) Key:SUPKOOSCJHTBAH-UHFFFAOYSA-N
(what is this?)  (verify)

Adefovir dipivoxil, previously called bis-POM PMEA, with trade names Preveon and Hepsera, is an orally-administered nucleotide analog reverse transcriptase inhibitor (ntRTI).

Uses

It is used for treatment of hepatitis B and herpes simplex virus infection.

It is a failed treatment for HIV.

History

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

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

1. Marcellin P; Chang TT; Lim SG; et al. (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. {{cite journal}}: Unknown parameter |author-separator= ignored (help); Unknown parameter |month= ignored (help)
2. Manolakopoulos S; Bethanis S; Koutsounas S; et al. (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. {{cite journal}}: Unknown parameter |author-separator= ignored (help); Unknown parameter |month= ignored (help)
3. ^ ADHOC International Steering Committee (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. {{cite journal}}: Unknown parameter |month= ignored (help)
4. Fisher EJ; Chaloner K; Cohn DL; et al. (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. {{cite journal}}: Unknown parameter |author-separator= ignored (help); Unknown parameter |month= ignored (help)

External links

• Hepsera web site
• CID 60172 from PubChem - Adefovir dipivoxil

• Gilead Sciences
• Reverse transcriptase inhibitors
• Purines
• Phosphonic acids