Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/10/02 16:36:06」(JST)

wiki en

Entecavir INN /ɛnˈtɛkəvɪər/ en-TEK-a-vir, abbreviated ETV, is an oral antiviral drug used in the treatment of hepatitis B infection. It is marketed under the trade names Baraclude (BMS) and Entaliv (DRL).

Entecavir is a nucleoside analog^[2] (more specifically, a guanosine analogue) that inhibits reverse transcription, DNA replication and transcription in the viral replication process. The drug's manufacturer claims that entecavir is more efficacious than previous agents used to treat hepatitis B (lamivudine and adefovir).

Entecavir was approved by the U.S. FDA in March 2005.

Uses

Entecavir is used to treat chronic hepatitis B. It also helps prevent the hepatitis B virus from multiplying and infecting new liver cells. Entecavir is also indicated for the treatment of chronic hepatitis B in adults with HIV/AIDS infection. However, entecavir is not active against HIV.

Clinical Trials

The clinical efficacy of entecavir has been studied in several randomized, double-blind, multicentre trials. Oral entecavir was an effective and generally well tolerated treatment.^[3]

History

1992: SQ-34676 at Squibb as part of anti-herpes virus program^[4]
1997: BMS 200475 developed at BMS pharmaceutical research institute as antiviral nucleoside analogue à Activity demonstrated against HBV, HSV-1, HCMV, VZV in cell lines & no or little activity against HIV or influenza^[5]
Superior activity observed against HBV pushed research towards BMS 200475, its base analogues and its enantiomer against HBV in HepG2.2.15 cell line^[5]
Comparison to other NAs, proven more selective potent inhibitor of HBV by virtue of being Guanine NA^[6]
1998: Inhibition of hepadnaviral polymerases was demonstrated in vitro in comparison to a number of NAs-TP^[7]
Metabolic studies showed more efficient phosphorylation to triphosphate active form^[8]
3 year treatment of woodchuck model of CHB à sustained antiviral efficacy and prolonged life spans without detectable emergence of resistance^[9]
Efficacy # LVD resistant HBV replication in vitro^[10]
Superior activity compared to LVD in vivo for both HBeAg+ & HBeAg− patients^[11]^[12]
Efficacy in LVD refractory CHB patients^[13]

References

^ “BARACLUDE^® (entecavir) Tablets for Oral Use & Oral Solution. U.S. Full Prescribing Information.” Bristol-Myers Squibb Company, 2005. Revised December 2013. [1]
^ Sims KA, Woodland AM (December 2006). "Entecavir: a new nucleoside analog for the treatment of chronic hepatitis B infection". Pharmacotherapy 26 (12): 1745–57. doi:10.1592/phco.26.12.1745. PMID 17125436.
^ Scott LJ, Keating GM.[2].Drugs 2009;69(8):1003-1033. doi:10.2165/00003495-200969080-00005.
^ Slusarchyk, W. A., A. K. Field, J. A. Greytok, P. Taunk, A. V. Tooumari, M. G. Young, and R. Zahler. 4-Hydroxy-3-(hydroxymethyl)-2-methylcyclopentyl purines and pyrimidines, a novel class of anti-herpesvirus agents. Abstract from the Fifth International Conference on Antiviral Research. Antivir Res 1992.17(Suppl. 1):98
^ ^a ^b Bisacchi, G. S., S. T. Chao, C. Bachard, J. P. Daris, S. F. Innaimo, J. A. Jacobs, O. Kocy, P. Lapointe, A. Martel, Z. Merchant, W. A. Slusarchyk, J. E. Sundeen, M. G. Young, R. Colonno, and R. Zahler. BMS-200475, a novel carbocyclic 29-deoxyguanosine analog with potent and selective antihepatitis B virus activity in vitro. Bioorg. Med. Chem. Lett. 1997. 7:127–132
^ Innaimo S F, Seifer M, Bisacchi G S, Standring D N, Zahler R, Colonno R J. Identification of BMS-200475 as a Potent and Selective Inhibitor of Hepatitis B Virus. Antimicrob. Agents Chemother. 1997. 41(7): 1444–1448
^ Seifer, M., R. K. Hamatake, R. J. Colonno, and D. N. Standring. In vitro inhibition of hepadnavirus polymerases by the triphosphates of BMS-200475 and lobucavir. Antimicrob. Agents Chemother. 1998. 42:3200–3208
^ Yamanaka, G., T. Wilson, S. Innaimo, G. S. Bisacchi, P. Egli, J. K. Rinehart, R. Zahler, and R. J. Colonno. Metabolic studies on BMS-200475, a new antiviral compound active against hepatitis B virus. Antimicrob. Agents Chemother. 1999. 43:190–193
^ Colonno, R. J., E. V. Genovesi, I. Medina, L. Lamb, S. K. Durham, M. L. Huang, L. Corey, M. Littlejohn, S. Locarnini, B. C. Tennant, B. Rose, and J. M. Clark. Long-term entecavir treatment results in sustained antiviral efficacy and prolonged life span in the woodchuck model of chronic hepatitis infection. J. Infect. Dis. 2001.184:1236–1245
^ Levine, S., D. Hernandez, G. Yamanaka, S. Zhang, R. Rose, S. Weinheimer, and R. J. Colonno. Efficacies of entecavir against lamivudine-resistant hepatitis B virus replication and recombinant polymerases in vitro. Antimicrob. Agents Chemother. 2002.46:2525–2532
^ Chang, T. T. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. N. Engl. J. Med. 2006. 354:1001–1010
^ Lai, C. L. et al. Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B. N. Engl. J.Med. 2006. 354:1011–1020.
^ Sherman, M., C. Yurdaydin, J. Sollano, M. Silva, Y. F. Liaw, J. Cianciara, A. Boron-Kaczmarska, P. Martin, Z. Goodman, R. J. Colonno, A. Cross, G. Denisky, B. Kreter, R. Hindes, and the AI463026 Behold Study Group. Entecavir for the treatment of lamivudine-refractory, HBeAg-positive chronic hepatitis B. Gastroenterology 2006. 130:2039–2049.

External links

PubMed Health page on Entecavir
Baraclude U.S. website

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 慢性B型肝炎ウイルス感染の治療におけるエンテカビル entecavir 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. HIV感染患者における慢性B型肝炎の治療 treatment of chronic hepatitis b in the hiv infected patient

English Journal

Review article: nucleos(t)ide analogues in patients with chronic hepatitis B virus infection and chronic kidney disease.

Pipili C, Cholongitas E, Papatheodoridis G.SourceDepartment of Nephrology, Laiki Merimna, Athens, Greece.
Alimentary pharmacology & therapeutics.Aliment Pharmacol Ther.2014 Jan;39(1):35-46. doi: 10.1111/apt.12538. Epub 2013 Oct 29.
BACKGROUND: The treatment of chronic hepatitis B (CHB) in patients with chronic kidney disease (CKD) is based on nucleoside (lamivudine, telbivudine, entecavir) or nucleotide (adefovir, tenofovir) analogues (NAs), but it may be complex and the information is scarce. Entecavir and tenofovir represent
PMID 24299322

Long-Term Efficacy of Entecavir Plus Adefovir Combination Therapy versus Entecavir Monotherapy in Adefovir Refractory Chronic Hepatitis B Patients with Prior Lamivudine Resistance.

Seo SY, Kim IH, Sohn JY, Lee S, Kim SH, Kim SW, Lee SO, Lee ST, Kim DG.SourceDepartment of Internal Medicine, Research Institute of Clinical Medicine, Chonbuk National University Medical School and Hospital, Jeonju, South Korea.
Intervirology.Intervirology.2014;57(1):8-16. doi: 10.1159/000353851. Epub 2013 Aug 24.
Objectives: We investigated the long-term efficacy of entecavir (ETV) + adefovir (ADV) combination therapy versus ETV monotherapy in lamivudine (LAM)-resistant chronic hepatitis B (CHB) patients who failed to respond to ADV rescue therapy. Methods: A total of 91 ADV refractory patients with prior LA
PMID 23988634

Anti-HBs seroconversion during treatment with entecavir in a patient with chronic hepatitis B virus infection on hemodialysis.

Spaziante M, Biliotti E, Grieco S, Palazzo D, Esvan R, Taliani G.SourceClinica Malattie Infettive e Tropicali, Sapienza University of Rome, Rome, Italy.
Journal of medical virology.J Med Virol.2014 Jan;86(1):139-43. doi: 10.1002/jmv.23795. Epub 2013 Oct 17.
Hepatitis B (HBV) virus infection is one of the most important causes of liver disease in patients with end-stage renal failure on hemodialysis. The natural history of chronic HBV infection acquired in childhood starts with an immune tolerant phase, followed by an immune clearance phase that may lea
PMID 24136393

Japanese Journal

Prospective study of reactivation of hepatitis B virus in patients with rheumatoid arthritis who received immunosuppressive therapy : evaluation of both HBsAg-positive and HBsAg-negative cohorts

TAMORI Akihiro,KOIKE Tatsuya,GOTO Hitoshi,WAKITANI Shigeyuki,TADA Masahiro,MORIKAWA Hiroyasu,ENOMOTO Masaru,INABA Masaaki,NAKATANI Tatsuya,HINO Masayuki,KAWADA Norifumi
Journal of gastroenterology 46(4), 556-564, 2011-04-01
NAID 10029028861

Development and Validation of a Stability-indicating Capillary Zone Electrophoretic Method for the Assessment of Entecavir and Its Correlation with Liquid Chromatographic Methods

DALMORA Sergio Luiz,NOGUEIRA Daniele Rubert,D'AVILA Felipe Bianchini,SOUTO Ricardo Bizogne,LEAL Diogo Paim
Analytical sciences : the international journal of the Japan Society for Analytical Chemistry 27(3), 265-270, 2011-03-10
NAID 10027906166

核酸アナログとインターフェロンの併用療法 (特集 B型肝炎に対する新治療戦略)

南祐仁
消化器内科 53(3), 316-320, 2011-09
NAID 40019027660

Related Pictures

★リンクテーブル★

リンク元	「エンテカビル」
拡張検索	「entecavir hydrate」

「エンテカビル」

Entecavir
Systematic (IUPAC) name
	2-Amino-9-[(1S,3R,4S)-4-hydroxy-3-(hydroxymethyl)-2-methylidenecyclopentyl]-6,9-dihydro-3H-purin-6-one
Clinical data
Trade names	Baraclude
AHFS/Drugs.com	monograph
MedlinePlus	a605028
Licence data	EMA:Link, US FDA:link
Pregnancy cat.	AU: B3; US: C;
Legal status	AU: Prescription Only (S4); CA: ℞-only; UK: POM; US: ℞-only;
Routes	Oral
Pharmacokinetic data
Bioavailability	n/a (≥70)
Protein binding	13% (in vitro)
Metabolism	negligible/nil
Half-life	128–149 hours
Excretion	Renal 62–73%
Identifiers
CAS number	142217-69-4
ATC code	J05AF10
PubChem	CID 153941
DrugBank	DB00442
ChemSpider	135679
UNII	NNU2O4609D
KEGG	D04008
ChEBI	CHEBI:59902
ChEMBL	CHEMBL713
Chemical data
Formula	C12H15N5O3
Mol. mass	277.279 g/mol
	SMILES O=C2/N=C(\Nc1n(cnc12)[C@@H]3C(=C)/[C@H](CO)[C@@H](O)C3)N;
	InChI InChI=1S/C12H15N5O3/c1-5-6(3-18)8(19)2-7(5)17-4-14-9-10(17)15-12(13)16-11(9)20/h4,6-8,18-19H,1-3H2,(H3,13,15,16,20)/t6-,7-,8-/m0/s1 ; Key:YXPVEXCTPGULBZ-WQYNNSOESA-N ;
(what is this?) (verify)

　　[★]

英: entecavir
化: エンテカビル水和物 entecavir hydrate
商: バラクルード
関: B型肝炎

特徴

グアノシン類似体

「entecavir hydrate」

　　[★]

エンテカビル水和物

関: entecavir

[1] “BARACLUDE^® (entecavir) Tablets for Oral Use & Oral Solution. U.S. Full Prescribing Information.” Bristol-Myers Squibb Company, 2005. Revised December 2013. [1]

[pmid17125436-2] Sims KA, Woodland AM (December 2006). "Entecavir: a new nucleoside analog for the treatment of chronic hepatitis B infection". Pharmacotherapy 26 (12): 1745–57. doi:10.1592/phco.26.12.1745. PMID 17125436.

[enteca-3] Scott LJ, Keating GM.[2].Drugs 2009;69(8):1003-1033. doi:10.2165/00003495-200969080-00005.

[4] Slusarchyk, W. A., A. K. Field, J. A. Greytok, P. Taunk, A. V. Tooumari, M. G. Young, and R. Zahler. 4-Hydroxy-3-(hydroxymethyl)-2-methylcyclopentyl purines and pyrimidines, a novel class of anti-herpesvirus agents. Abstract from the Fifth International Conference on Antiviral Research. Antivir Res 1992.17(Suppl. 1):98

[Bisacchi.2C_G._S._1997-5] Bisacchi, G. S., S. T. Chao, C. Bachard, J. P. Daris, S. F. Innaimo, J. A. Jacobs, O. Kocy, P. Lapointe, A. Martel, Z. Merchant, W. A. Slusarchyk, J. E. Sundeen, M. G. Young, R. Colonno, and R. Zahler. BMS-200475, a novel carbocyclic 29-deoxyguanosine analog with potent and selective antihepatitis B virus activity in vitro. Bioorg. Med. Chem. Lett. 1997. 7:127–132

[6] Innaimo S F, Seifer M, Bisacchi G S, Standring D N, Zahler R, Colonno R J. Identification of BMS-200475 as a Potent and Selective Inhibitor of Hepatitis B Virus. Antimicrob. Agents Chemother. 1997. 41(7): 1444–1448

[7] Seifer, M., R. K. Hamatake, R. J. Colonno, and D. N. Standring. In vitro inhibition of hepadnavirus polymerases by the triphosphates of BMS-200475 and lobucavir. Antimicrob. Agents Chemother. 1998. 42:3200–3208

[8] Yamanaka, G., T. Wilson, S. Innaimo, G. S. Bisacchi, P. Egli, J. K. Rinehart, R. Zahler, and R. J. Colonno. Metabolic studies on BMS-200475, a new antiviral compound active against hepatitis B virus. Antimicrob. Agents Chemother. 1999. 43:190–193

[9] Colonno, R. J., E. V. Genovesi, I. Medina, L. Lamb, S. K. Durham, M. L. Huang, L. Corey, M. Littlejohn, S. Locarnini, B. C. Tennant, B. Rose, and J. M. Clark. Long-term entecavir treatment results in sustained antiviral efficacy and prolonged life span in the woodchuck model of chronic hepatitis infection. J. Infect. Dis. 2001.184:1236–1245

[10] Levine, S., D. Hernandez, G. Yamanaka, S. Zhang, R. Rose, S. Weinheimer, and R. J. Colonno. Efficacies of entecavir against lamivudine-resistant hepatitis B virus replication and recombinant polymerases in vitro. Antimicrob. Agents Chemother. 2002.46:2525–2532

[11] Chang, T. T. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. N. Engl. J. Med. 2006. 354:1001–1010

[12] Lai, C. L. et al. Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B. N. Engl. J.Med. 2006. 354:1011–1020.

[13] Sherman, M., C. Yurdaydin, J. Sollano, M. Silva, Y. F. Liaw, J. Cianciara, A. Boron-Kaczmarska, P. Martin, Z. Goodman, R. J. Colonno, A. Cross, G. Denisky, B. Kreter, R. Hindes, and the AI463026 Behold Study Group. Entecavir for the treatment of lamivudine-refractory, HBeAg-positive chronic hepatitis B. Gastroenterology 2006. 130:2039–2049.

匿名

検索

案内

案内

entecavir