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{{Short description|Chemical compound}}
{{Drugbox {{Drugbox
| Verifiedfields = changed | Verifiedfields = changed
| verifiedrevid = 456665883 | verifiedrevid = 477242223
| IUPAC_name = {methyl}phosphonic acid | IUPAC_name = {methyl}phosphonic acid
| image = Adefovir.svg | image = Adefovir.svg
| width = 208 | width = 215


<!--Clinical data--> <!--Clinical data-->
| tradename = | tradename = Hepsera
| Drugs.com = {{drugs.com|monograph|adefovir-dipivoxil}} | Drugs.com = {{drugs.com|monograph|adefovir-dipivoxil}}
| pregnancy_AU = B3
| pregnancy_US = C | pregnancy_US = C
| legal_status = Rx-only | legal_AU = S4
| legal_CA = Rx-only
| legal_UK = POM
| legal_US = Rx-only
| routes_of_administration = Oral | routes_of_administration = Oral


<!--Pharmacokinetic data--> <!--Pharmacokinetic data-->
| bioavailability = 59% | bioavailability = 59%
| protein_bound = | protein_bound = <4%
| metabolism = | metabolism =
| elimination_half-life = 7.5 hours | elimination_half-life = 7.5 hours
| excretion = Urine


<!--Identifiers--> <!--Identifiers-->
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| ATC_prefix = J05 | ATC_prefix = J05
| ATC_suffix = AF08 | ATC_suffix = AF08
| ATC_supplemental = | ATC_supplemental =
| PubChem = 60172 | PubChem = 60172
| DrugBank_Ref = {{drugbankcite|changed|drugbank}} | DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = APRD00781 | DrugBank = DB00718
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 54252 | ChemSpiderID = 54252
Line 33: Line 39:
| UNII_Ref = {{fdacite|correct|FDA}} | UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 6GQP90I798 | UNII = 6GQP90I798
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 2469
| KEGG_Ref = {{keggcite|correct|kegg}} | KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D02768 | KEGG = D02768
Line 39: Line 47:


<!--Chemical data--> <!--Chemical data-->
| C=8 | H=12 | N=5 | O=4 | P=1 | C=8 | H=12 | N=5 | O=4 | P=1
| molecular_weight = 273.186 g/mol
| smiles = O=P(O)(O)COCCn1c2ncnc(c2nc1)N | smiles = O=P(O)(O)COCCn1c2ncnc(c2nc1)N
| InChI = 1/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)
| InChIKey = SUPKOOSCJHTBAH-UHFFFAOYAL
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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) | StdInChI = 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)
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}} }}


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


==Uses== ==Uses==
It is used for treatment of ] <ref name="pmid12606735">{{cite journal |author=Marcellin P |title=Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B |journal=N. Engl. J. Med. |volume=348 |issue=9 |pages=808–16 |year=2003 |month=February |pmid=12606735 |doi=10.1056/NEJMoa020681 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=12606735&promo=ONFLNS19 |author-separator=, |author2=Chang TT |author3=Lim SG |display-authors=3 |last4=Tong |first4=Myron J. |last5=Sievert |first5=William |last6=Shiffman |first6=Mitchell L. |last7=Jeffers |first7=Lennox |last8=Goodman |first8=Zachary |last9=Wulfsohn |first9=Michael S.}}</ref><ref name="pmid17988233">{{cite journal |author=Manolakopoulos S |title=Long-term therapy with adefovir dipivoxil in hepatitis B e antigen-negative patients developing resistance to lamivudine |journal=Aliment. Pharmacol. Ther. |volume=27 |issue=3 |pages=266–73 |year=2008 |month=February |pmid=17988233 |doi=10.1111/j.1365-2036.2007.03567.x |url=http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0269-2813&date=2008&volume=27&issue=3&spage=266 |author-separator=, |author2=Bethanis S |author3=Koutsounas S |display-authors=3 |last4=Goulis |first4=J. |last5=Vlachogiannakos |first5=J. |last6=Christias |first6=E. |last7=Saveriadis |first7=A. |last8=Pavlidis |first8=C. |last9=Triantos |first9=C.}}</ref> and ] infection. <ref name="pmid12444940"/> It is used for treatment of ].<ref name="pmid12606735">{{cite journal | vauthors = Marcellin P, Chang TT, Lim SG, Tong MJ, Sievert W, Shiffman ML, Jeffers L, Goodman Z, Wulfsohn MS, Xiong S, Fry J, Brosgart CL | display-authors = 6 | title = Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B | journal = The New England Journal of Medicine | volume = 348 | issue = 9 | pages = 808–16 | date = February 2003 | pmid = 12606735 | doi = 10.1056/NEJMoa020681 | url = https://scholarscompass.vcu.edu/cgi/viewcontent.cgi?article=1053&context=intmed_pubs | doi-access = free }}</ref><ref name="pmid17988233">{{cite journal | vauthors = Manolakopoulos S, Bethanis S, Koutsounas S, Goulis J, Vlachogiannakos J, Christias E, Saveriadis A, Pavlidis C, Triantos C, Christidou A, Papatheodoridis G, Karamanolis D, Tzourmakliotis D | display-authors = 6 | title = Long-term therapy with adefovir dipivoxil in hepatitis B e antigen-negative patients developing resistance to lamivudine | journal = Alimentary Pharmacology & Therapeutics | volume = 27 | issue = 3 | pages = 266–73 | date = February 2008 | pmid = 17988233 | doi = 10.1111/j.1365-2036.2007.03567.x | doi-access = free }}</ref><ref name="pmid12444940"/><ref>{{cite web|title=US Adefovir Dipivoxil label|url=http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202051Orig1s000lbl.pdf|publisher=FDA|access-date=12 February 2017|date=April 2013}}</ref>


It is a failed treatment for ].<ref name="pmid12444940">{{cite journal |author= |title=A randomized placebo-controlled trial of adefovir dipivoxil in advanced HIV infection: the ADHOC trial |journal=HIV Med. |volume=3 |issue=4 |pages=229–38 |year=2002 |month=October |pmid=12444940 |doi= 10.1046/j.1468-1293.2002.00111.x|url=http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=1464-2662&date=2002&volume=3&issue=4&spage=229 |author1= ADHOC International Steering Committee}}</ref><ref name="pmid11546945">{{cite journal |author=Fisher EJ |title=The safety and efficacy of adefovir dipivoxil in patients with advanced HIV disease: a randomized, placebo-controlled trial |journal=AIDS |volume=15 |issue=13 |pages=1695–700 |year=2001 |month=September |pmid=11546945 |doi= 10.1097/00002030-200109070-00013|url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0269-9370&volume=15&issue=13&spage=1695 |author-separator=, |author2=Chaloner K |author3=Cohn DL |display-authors=3 |last4=Grant |first4=Lisa Bjorling |last5=Alston |first5=Beverly |last6=Brosgart |first6=Carol L. |last7=Schmetter |first7=Barry |last8=El-Sadr |first8=Wafaa M. |last9=Sampson |first9=James}}</ref> Trials of adefovir in patients with ] have not shown any clear benefits.<ref name="pmid12444940">{{cite journal | author = ADHOC International Steering Committee | title = A randomized placebo-controlled trial of adefovir dipivoxil in advanced HIV infection: the ADHOC trial | journal = HIV Medicine | volume = 3 | issue = 4 | pages = 229–38 | date = October 2002 | pmid = 12444940 | doi = 10.1046/j.1468-1293.2002.00111.x | doi-access = free }}</ref><ref name="pmid11546945">{{cite journal | vauthors = Fisher EJ, Chaloner K, Cohn DL, Grant LB, Alston B, Brosgart CL, Schmetter B, El-Sadr WM, Sampson J | display-authors = 6 | title = The safety and efficacy of adefovir dipivoxil in patients with advanced HIV disease: a randomized, placebo-controlled trial | journal = AIDS | volume = 15 | issue = 13 | pages = 1695–700 | date = September 2001 | pmid = 11546945 | doi = 10.1097/00002030-200109070-00013 | s2cid = 9425407 | doi-access = free }}</ref>


==History== ==History==
Adefovir was invented in the Institute of Organic Chemistry and Biochemistry, ] by ], and the drug was developed by ] for ] with the brand name '''Preveon'''. However, in November 1999, an expert panel advised the U.S. ] (FDA) not to approve the drug due to concerns about the severity and frequency of kidney toxicity when dosed at 60 or 120&nbsp;mg. The FDA followed that advice, refusing to approve adefovir as a treatment for HIV. Adefovir was invented in the Institute of Organic Chemistry and Biochemistry, ] by ], and the drug was developed by ] for HIV with the brand name Preveon. However, in November 1999, an expert panel advised the U.S. ] (FDA) not to approve the drug due to concerns about the severity and frequency of kidney toxicity when dosed at 60 or 120&nbsp;mg. The FDA followed that advice, refusing to approve adefovir as a treatment for HIV.{{cn|date=November 2022}}


] discontinued its development for HIV treatment in December 1999 but continued to develop the drug for ] (HBV), where it is effective with a much lower dose of 10&nbsp;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'''. 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&nbsp;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 European Union in March 2003.{{cn|date=November 2022}}

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== ==Mechanism of action==
] ]
Adefovir works by blocking ], an enzyme that is crucial for the ] virus (HBV) to reproduce in the body. Adefovir works by blocking ], an enzyme crucial for the 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 ]s (primarily ALT) or histologically active disease.


⚫ The main benefit of adefovir over ] (the first NRTI approved for the treatment of HBV) is that it takes a much longer period of time for the virus to develop resistance to it.
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 ]s (primarily ALT) or histologically active disease.


⚫ Adefovir dipivoxil contains two ] units, making it a ] form of adefovir.
⚫ The main benefit of adefovir over ] (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.


⚫ == References ==
⚫ Adefovir dipivoxil contains two ] units, making it a ] form of Adefovir.

⚫ ==References==
{{Reflist}} {{Reflist}}


==External links== == External links ==
⚫ * {{PubChem}} - Adefovir dipivoxil
*
⚫ *{{PubChem|60172}} - Adefovir dipivoxil


{{Antivirals}} {{Antivirals}}
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] ]
] ]

]
]
]
]
]

Latest revision as of 15:12, 20 November 2023

Chemical compound Pharmaceutical compound
Adefovir
Clinical data
Trade namesHepsera
AHFS/Drugs.comMonograph
Pregnancy
category
  • AU: B3
Routes of
administration		Oral
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability59%
Protein binding<4%
Elimination half-life7.5 hours
ExcretionUrine
Identifiers
IUPAC name
  • {methyl}phosphonic acid
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
NIAID ChemDB
CompTox Dashboard (EPA)
ECHA InfoCard100.106.235 Edit this at Wikidata
Chemical and physical data
FormulaC8H12N5O4P
Molar mass273.189 g·mol
3D model (JSmol)
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 is a prescription medicine used to treat (chronic) infections with hepatitis B virus. A prodrug form of 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

It is used for treatment of hepatitis B.

Trials of adefovir in patients with HIV have not shown any clear benefits.

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 European Union in March 2003.

Mechanism of action

Adefovir dipivoxil

Adefovir works by blocking reverse transcriptase, an enzyme crucial for the 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 HBV) is that it takes a much longer period of time for the virus to develop resistance to it.

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

References

  1. Marcellin P, Chang TT, Lim SG, Tong MJ, Sievert W, Shiffman ML, et al. (February 2003). "Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B". The New England Journal of Medicine. 348 (9): 808–16. doi:10.1056/NEJMoa020681. PMID 12606735.
  2. Manolakopoulos S, Bethanis S, Koutsounas S, Goulis J, Vlachogiannakos J, Christias E, et al. (February 2008). "Long-term therapy with adefovir dipivoxil in hepatitis B e antigen-negative patients developing resistance to lamivudine". Alimentary Pharmacology & Therapeutics. 27 (3): 266–73. doi:10.1111/j.1365-2036.2007.03567.x. PMID 17988233.
  3. ^ ADHOC International Steering Committee (October 2002). "A randomized placebo-controlled trial of adefovir dipivoxil in advanced HIV infection: the ADHOC trial". HIV Medicine. 3 (4): 229–38. doi:10.1046/j.1468-1293.2002.00111.x. PMID 12444940.
  4. "US Adefovir Dipivoxil label" (PDF). FDA. April 2013. Retrieved 12 February 2017.
  5. Fisher EJ, Chaloner K, Cohn DL, Grant LB, Alston B, Brosgart CL, 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. S2CID 9425407.

External links

DNA virus antivirals (primarily J05, also S01AD and D06BB)
Baltimore I
Herpesvirus
DNA-synthesis
inhibitor
TK activated
Purine analogue
Pyrimidine analogue
Not TK activated
Other
HPV/MC
Vaccinia
Poxviridae
Hepatitis B (VII)
Multiple/general
Nucleic acid inhibitors
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