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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

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

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 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

^ 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.
^ 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.
^ ^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.
^ 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

Hepsera web site
PubChem 60172 - Adefovir dipivoxil

UpToDate Contents

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1. 慢性B型肝炎ウイルス感染の治療におけるアデホビルジピボキシル adefovir dipivoxil in the treatment of chronic hepatitis b virus infection
2. B型肝炎のマネージメントの概要および症例 overview of the management of hepatitis b and case examples
3. 小児および思春期におけるB型肝炎ウイルス感染の概要 overview of hepatitis b virus infection in children and adolescents
4. 慢性B型肝炎ウイルス感染の治療におけるテルビブジン telbivudine in the treatment of chronic hepatitis b virus infection
5. HIV感染患者に対するB型肝炎治療のための抗ウイルス剤 antiviral medications for the treatment of hepatitis b in the hiv infected patient

English Journal

Bisamidate Prodrugs of 2-Substituted 9-[2-(Phosphonomethoxy)ethyl]adenine (PMEA, adefovir) as Selective Inhibitors of Adenylate Cyclase Toxin from Bordetella pertussis.

Česnek M1, Jansa P1, Šmídková M1, Mertlíková-Kaiserová H1, Dračínský M1, Brust TF2, Pávek P3,4, Trejtnar F3, Watts VJ2, Janeba Z5.
ChemMedChem.ChemMedChem.2015 Aug;10(8):1351-64. doi: 10.1002/cmdc.201500183. Epub 2015 Jul 1.
Novel small-molecule agents to treat Bordetella pertussis infections are highly desirable, as pertussis (whooping cough) remains a serious health threat worldwide. In this study, a series of 2-substituted derivatives of 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA, adefovir), in their isopropyl ester
PMID 26136378

Current treatment of hepatitis B virus infections.

De Clercq E1.
Reviews in medical virology.Rev Med Virol.2015 Jul 23. doi: 10.1002/rmv.1849. [Epub ahead of print]
Chronic hepatitis B virus (HBV) infection remains an important global burden with an estimated 240 million HBV carriers worldwide and more than half a million people dying annually from the consequences of the HBV infection. Besides interferon and pegylated interferon, there are five antiviral drugs
PMID 26205627

A novel baseline hepatitis B virus sequencing-based strategy for predicting adefovir antiviral response.

Wang YW1, Shan X2, Huang Y3, Deng H3, Huang WX4, Zhang DZ5, Chen J3, Tang N3, Shan YL5, Guo JJ6, Huang A7.
Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.Infect Genet Evol.2015 Jul;33:269-76. doi: 10.1016/j.meegid.2015.05.014. Epub 2015 May 14.
Adefovir dipivoxil (ADV) is used as first-line monotherapy or rescue therapy in chronic hepatitis B (CHB) patients. In this study, we sought to identify nucleotide changes in the reverse transcriptase (RT) of hepatitis B virus (HBV) at baseline and explore their predictive value for ADV antiviral re
PMID 25983054

Japanese Journal

B型慢性肝炎に対する核酸アナログ療法ラミブジン,アデホビル (新時代のウイルス性肝炎学--基礎・臨床研究の進歩) -- (B型慢性肝炎に対する治療学の進歩)

宮島一郎,佐田通夫
日本臨床 69(-) (999), 492-497, 2011-05
NAID 40018838525

アデホビルによる腎障害の検討

小関至,狩野吉康,赤池淳,木村睦海,荒川智宏,中島知明,桑田靖昭,大村卓味,佐藤隆啓,豊田成司
肝臓 52(2), 102-111, 2011-02-25
アデホビルは容量依存性に腎障害を生じることが知られており，現在では10 mg/日が適正使用量とされた．この投与量を遵守しても長期投与では一定の割合で腎障害が出現することが海外より示されているが，本邦におけるアデホビルの腎機能に与える影響については未だ不明である．今回，われわれは3年以上継続投与できた核酸アナログ投与例，3年以上経過観察可能であったHBV無症候性キャリア（無治療例）を対象とし，腎障害 …
NAID 10029285001

Related Pictures

★リンクテーブル★

リンク元	「アデホビル」「アデフォビルピボキシル」「アデホビルジピボキシル」

「アデホビル」

Adefovir
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
ATC code	J05AF08
PubChem	CID 60172
DrugBank	DB00718
ChemSpider	54252
UNII	6GQP90I798
KEGG	D02768
ChEMBL	CHEMBL484
NIAID ChemDB	028595
Chemical data
Formula	C8H12N5O4P
Mol. mass	273.186 g/mol
	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 ;
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