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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/11/25 01:14:32」(JST)

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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 ^[1]^[2] and herpes simplex virus infection. ^[3]^[4]

Trials of adefovir in patients with HIV have not shown any clear benefits.^[3]^[5]

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

^ 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.
^ "US Adefovir Dipivoxil label" (PDF). FDA. April 2013. Retrieved 12 February 2017.
^ 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

CID {{{1}}} from PubChem - 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
4. 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
5. B型肝炎と妊娠 hepatitis b and pregnancy

English Journal

Inhibitory effects of p-aminohippurate and probenecid on the renal clearance of adefovir and benzylpenicillin as probe drugs for organic anion transporter (OAT) 1 and OAT3 in humans.

Maeda K1, Tian Y1, Fujita T2, Ikeda Y2, Kumagai Y2, Kondo T3, Tanabe K3, Nakayama H3, Horita S3, Kusuhara H1, Sugiyama Y4.
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.Eur J Pharm Sci.2014 Aug 1;59C:94-103. doi: 10.1016/j.ejps.2014.04.004. Epub 2014 Apr 18.
Probe substrates for, and inhibitors of, specific transporters are desired to evaluate quantitatively the in vivo functions of transporters in humans. Based on published data, adefovir and benzylpenicillin were selected as organic anion transporter (OAT) 1- and OAT3-selective probe substrates, respe
PMID 24747579

The Impact of the Hepatitis B Virus Polymerase rtA181T Mutation on Replication and Drug Resistance Is Potentially Affected by Overlapping Changes in Surface Gene.

Ahn SH1, Park YK2, Park ES2, Kim JH3, Kim DH1, Lim KH1, Jang MS1, Choe WH3, Ko SY3, Sung IK3, Kwon SY3, Kim KH4.
Journal of virology.J Virol.2014 Jun 15;88(12):6805-6818. Epub 2014 Apr 2.
The emergence of drug-resistant hepatitis B virus (HBV) is a major problem for antiviral treatment in chronic hepatitis B infection. In this study, we analyzed the evolution of drug-resistant mutations and characterized the effects of the rtA181T and rtI233V mutations on viral replication and drug r
PMID 24696492

Generation of a human hepatoma cell line supporting efficient replication of a lamivudine resistant hepatitis B virus.

Zhang Y1, Zhang Y1, Kang Y1, Wang J1, Liu H1, Zhu H1, Qin Y1, Mao R1, Lin X2, Lu M3, Zhang J4.
Journal of virological methods.J Virol Methods.2014 Jun;201:51-6. doi: 10.1016/j.jviromet.2014.02.008. Epub 2014 Feb 28.
Emergence of lamivudine (LAM) resistance causes treatment failure in patients with chronic hepatitis B and compromise the efficacy of subsequent salvage therapies with other nucleot(s)ide analogs (NAs). Establishment of cell-based assays supporting LAM-resistant hepatitis B virus (HBV) replication w
PMID 24583110

Japanese Journal

臨床室両踵骨不全骨折を契機に診断されたアデホビルピボキシルによる骨軟化症の1例

整形外科 = Orthopedic surgery 68(7), 649-653, 2017-07
NAID 40021251302

アデホビルにてFanconi症候群を来たしたB型慢性肝炎の1例

日本内科学会雑誌 105(6), 1026-1033, 2016
NAID 130005696735

Bone Histology of Two Cases with Osteomalacia Related to Low-dose Adefovir

Internal Medicine 55(20), 3013-3019, 2016
NAID 130005429974

Related Pictures

★リンクテーブル★

リンク元	「アデホビル」「ADV」

「アデホビル」

Adefovir
Clinical data
Trade names	Hepsera
AHFS/Drugs.com	Monograph
Pregnancy; category	AU: B3; US: C (Risk not ruled out); ;
Routes of; administration	Oral
ATC code	J05AF08 (WHO);
Legal status
Legal status	AU: S4 (Prescription only); CA: ℞-only; UK: POM (Prescription only); US: ℞-only;
Pharmacokinetic data
Bioavailability	59%
Protein binding	<4%
Biological half-life	7.5 hours
Excretion	Urine
Identifiers
	IUPAC name {[2-(6-amino-9H-purin-9-yl)ethoxy]methyl}phosphonic acid;
CAS Number	106941-25-7 ;
PubChem CID	60172;
DrugBank	DB00718 ;
ChemSpider	54252 ;
UNII	6GQP90I798;
KEGG	D02768 ;
ChEBI	CHEBI:2469 ;
ChEMBL	CHEMBL484 ;
NIAID ChemDB	028595;
ECHA InfoCard	100.106.235
Chemical and physical data
Formula	C8H12N5O4P
Molar mass	273.186 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 ;
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　　[★]

英: adefovir ADV
同: アデフォビル
化: アデホビルジピボキシル、アデホビルピボキシル、アデフォビルピボキシル　 adefovir dipivoxil
商: ヘプセラ

特徴

アデニン類似体

「ADV」

　　[★] アデホビル adefovir

[pmid12606735-1] 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.

[pmid17988233-2] 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.

[pmid12444940-3] 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] "US Adefovir Dipivoxil label" (PDF). FDA. April 2013. Retrieved 12 February 2017.

[pmid11546945-5] 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.

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adefovir