WordNet

a Cox-2 inhibitor (trade name Bextra) that relieves pain and inflammation without harming the digestive tract (同)Bextra

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/09/03 06:38:53」(JST)

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Valdecoxib is a non-steroidal anti-inflammatory drug (NSAID) used in the treatment of osteoarthritis, rheumatoid arthritis, and painful menstruation and menstrual symptoms. It is a cyclooxygenase-2 selective inhibitor.

Valdecoxib was manufactured and marketed under the brand name Bextra by G. D. Searle & Company. It was approved by the United States Food and Drug Administration on November 20, 2001,^[1] and was available by prescription in tablet form until 2005, when it was removed from the market due to concerns about possible increased risk of heart attack and stroke.

Uses until 2005

In the United States, the Food and Drug Administration (FDA) approved valdecoxib for the treatment of osteoarthritis, adult rheumatoid arthritis, and primary dismennorhea.^[2]

Valdecoxib was also used off-label for controlling acute pain and various types of surgical pain, though Pfizer was penalized for promoting such uses in US.^[2]

Side-effects and withdrawal from market

On April 7, 2005, Pfizer withdrew Bextra from the U.S. market on recommendation by the FDA, citing an increased risk of heart attack and stroke and also the risk of a serious, sometimes fatal, skin reaction. This was a result of recent attention to prescription NSAIDs, such as Merck's Vioxx. Other reported side-effects were angina and Stevens–Johnson syndrome.

Pfizer first acknowledged cardiovascular risks associated with Bextra in October 2004. The American Heart Association soon after was presented with a report indicating patients using Bextra while recovering from heart surgery were 2.19 times more likely to suffer a stroke or heart attack than those taking placebos.

Recently in a large study published in JAMA 2006, valdecoxib appears less adverse for renal (kidney) disease and heart arrhythmia compared to Vioxx, however elevated renal risks were slightly suggested.^[3]

2009 settlement for off-label uses promotions

On September 2, 2009, the United States Department of Justice fined Pfizer $2.3 billion after one of its subsidiaries, Pharmacia & UpJohn Company, pled guilty to marketing four drugs including Bextra "with the intent to defraud or mislead."^[4] Pharmacia & UpJohn admitted to criminal conduct in the promotion of Bextra, and agreed to pay the largest criminal fine ever imposed in the United States for any matter, $1.195 billion.^[5] A former Pfizer district sales manager was indicted and sentenced to home confinement for destroying documents regarding the illegal promotion of Bextra.^[6]^[7] In addition, a Regional Manager pled guilty to distribution of a mis-branded product, and was fined $75,000 and twenty-four months on probation.^[8]

The remaining $1 billion of the fine was paid to resolve allegations under the civil False Claims Act case and is the largest civil fraud settlement against a pharmaceutical company. Six whistle-blowers were awarded more than $102 million for their role in the investigation.^[9] Former Pfizer sales representative John Kopchinski acted as a qui tam relator and filed a complaint in 2004 outlining the illegal conduct in the marketing of Bextra.^[10] Kopchinski was awarded $51.5 million for his role in the case because the improper marketing of Bextra was the largest piece of the settlement at $1.8 billion.^[11]

Synthesis

Source:^[12]

Assay of Valdecoxib^[13]

Several HPLC-UV methods have been reported for valdecoxib estimation in biological samples like human urine ^[14], plasma ^[15], ^[16]. Valdecoxib has analytical methods for bioequivalence studies ^[17], ^[18], metabolite determination ^[19], ^[20], ^[21] and estimation of formulation ^[22], HPTLC method for simultaneous estimation in tablet dosage form ^[23].

References

^ Thomson Micromedex. "Valdecoxib. U.S. FDA Drug Approval." Last accessed June 8, 2007.
^ ^a ^b "Pfizer to pay $2.3 billion to resolve criminal and civil health care liability relating to fraudulent marketing and the payment of kickbacks". Stop Medicare Fraud, US Dept of Health & Human Svc, and of Justice. http://www.stopmedicarefraud.gov/pfizerfactsheet.html. Retrieved 2012-07-04.
^ "Adverse Effects of Cyclooxygenase-2 Inhibitors on Renal and Arrhythmia Events: Meta-Analysis of Randomized Trials", (JAMA 2006, by Zhang JJ, Ding EL, Song Y.).
^ http://news.bbc.co.uk/2/hi/business/8234533.stm Pfizer agrees record fraud fine
^ http://www.usdoj.gov/usao/ma/Press%20Office%20-%20Press%20Release%20Files/Sept2009/PharmaciaPlea.html
^ http://www.usdoj.gov/usao/ma/Press%20Office%20-%20Press%20Release%20Files/Mar2009/FarinaconvictionPR.html
^ http://industry.bnet.com/pharma/10002882/pfizers-off-label-bextra-team-were-called-the-highlanders/
^ http://www.usdoj.gov/usao/ma/Press%20Office%20-%20Press%20Release%20Files/June2009/HollowayMarySentencingPR.html
^ http://www.fbi.gov/pressrel/pressrel09/justice_090209.htm
^ http://www.phillipsandcohen.com/CM/NewsSettlements/NewsSettlements536.asp
^ http://www.phillipsandcohen.com/CM/NewsSettlements/NewsSettlements531.asp
^ Talley, J. J.; Brown, D. L.; Carter, J. S.; Graneto, M. J.; Koboldt, C. M.; Masferrer, J. L.; Perkins, W. E.; Rogers, R. S. et al. (2000). "4-[5-Methyl-3-phenylisoxazol-4-yl]- benzenesulfonamide, Valdecoxib: A Potent and Selective Inhibitor of COX-2". Journal of Medicinal Chemistry 43 (5): 775. doi:10.1021/jm990577v. PMID 10715145. edit
^ Prafulla Kumar Sahu and M. Mathrusri Annapurna, Analytical method development by liquid chromatography, LAP Lambert Academic Publisher, Germany, 2011 ISBN 3-8443-2869-6.
^ Zhang J Y, Fast D M and Breau A P, J Chromatogr B Analyt Technol Biomed Life Sci., 2003, 785(1), 123-134
^ Ramakrishna N V S, Vishwottam K N; Wishu S and Koteshwara M, J Chromatogr B Analyt Technol Biomed Life Sci., 2004, 802(2), 271.
^ Sane R T, Menon S, Deshpande A Y and Jain A, Chromatogr., 2005, 61(3-4), 137-141.
^ Prafulla Kumar Sahu*, K. Ravi Sankar and M. Mathrusri Annapurna, Determination of Valdecoxib in human plasma using Reverse Phase HPLC”, E-Journal of Chemistry, 2011, 8(2), 875-881.
^ Mandal U, Jayakumar M, Ganesan M, Nandi S, Pal T K, Chakraborty M K, Roy Chowdhary A. and Chattoraj T K, Indian Drugs, 2004, 41, 59.
^ Zhang J.Y, Fast D.M and Breau, A.P, J Pharm Biomed Anal., 2003, 33, 61.
^ Werner U, Werner D, Hinz B, Lanbrecht C and Brune K, J Biomed Chromatogr., 2004, 19, 113.
^ Zhang J V, Fast D M and Breau A P, J Chromatogr B Anal Technol Biomed Life Sci., 2003, 785, 123.
^ Sutariya V B, Rajashree M, Sankalia M G. and Priti P, Indian J Pharm Sci., 2004, 93, 112.
^ Gandhimathi M, Ravi T K, Shukla Nilima and Sowmiya G, Indian J Pharm Sci., 2007, 69(1), 145-147.

External links

FDA Alert on Bextra withdrawal
Large systematic review of adverse renal and arrhythmia risk of valdcoxib and other COX-2 inhibitors, JAMA 2006

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. COX-2阻害剤および胃十二指腸障害：大規模臨床試験 cox 2 inhibitors and gastroduodenal toxicity major clinical trials
2. COX-2選択的阻害剤の概要 overview of selective cox 2 inhibitors
3. COX-2選択的阻害剤：有害な心血管系への影響 cox 2 selective inhibitors adverse cardiovascular effects
4. 避妊している女性におけるホルモン剤内服中の出血のマネージメント management of unscheduled bleeding in women using contraception
5. 内視鏡的逆行性胆管膵管造影（ERCP）後膵炎 post endoscopic retrograde cholangiopancreatography ercp pancreatitis

English Journal

Sulfonamides: a patent review (2008 - 2012).

Carta F, Scozzafava A, Supuran CT.SourceUniversità degli Studi di Firenze, Laboratorio di Chimica Bioinorganica , Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Florence) , Italy +39 0554573273 ; +39 055 4573385 ; claudiu.supuran@unifi.it.
Expert opinion on therapeutic patents.Expert Opin Ther Pat.2012 Jul;22(7):747-58. Epub 2012 Jun 15.
Introduction: The primary sulfonamide moiety is present in many clinically used drugs, such as diuretics (furosemide, indapamide, chlorthalidone, thiazides); carbonic anhydrase (CA) inhibitors (CAIs) (including acetazolamide, dichlorophenamide, dorzolamide and brinzolamide); antiepileptics (zonisam
PMID 22697257

Nonsteroidal anti-inflammatory drug-activated gene-1 plays a role in the impairing effects of cyclooxygenase inhibitors on gastric ulcer healing.

Colucci R, Antonioli L, Bernardini N, Ippolito C, Segnani C, Awwad O, Tuccori M, Blandizzi C, Scarpignato C, Fornai M.SourceInterdepartmental Centre for Research in Clinical Pharmacology and Experimental Therapeutics, University of Pisa, Via Roma 55, 56126, Pisa, Italy. c.blandizzi@virgilio.it.
The Journal of pharmacology and experimental therapeutics.J Pharmacol Exp Ther.2012 Jul;342(1):140-9. Epub 2012 Apr 10.
Nonsteroidal anti-inflammatory drugs (NSAIDs) can impair gastric ulcer healing. This study investigates the involvement of NSAID-activated gene-1 (NAG-1) in ulcer repair impairment by cyclooxygenase (COX) inhibitors. Gastric ulcers were induced in rats by acetic acid. Four days later, animals receiv
PMID 22495067

Japanese Journal

酸化的芳香化の制御を機軸とするヨード環化反応の開発

沖津貴志
YAKUGAKU ZASSHI 131(9), 1323-1327, 2011
… The utility of our methodology was demonstrated in the synthesis of valdecoxib and its 2,5-dihydro analogs. …
NAID 130001871938

Preparation, Characterization and in Vitro Dissolution Studies of Solid Systems of Valdecoxib with Chitosan

Vijaya Kumar Sengodan Gurusamy,Mishra Dina Nath
Chemical & pharmaceutical bulletin 54(8), 1102-1106, 2006-08-01
… In the present study, the solubilizing and amorphizing properties of Valdecoxib (a poorly water soluble anti inflammatory drug) with low molecular weight chitosan (a polymer), have been investigated. … Enhanced dissolution combined with its direct compression feasibility and anti ulcerogenic action results in low molecular weight chitosan for developing fast release oral solid dosage forms of valdecoxib. …
NAID 110004847226

Spray Dried Excipient Base : A Novel Technique for the Formulation of Orally Disintegrating Tablets

Mishra Dina Nath,Bindal Madhu,Singh Shailendra Kumar [他],VIJAYA KUMAR Sengodan Gurusamy
Chemical & pharmaceutical bulletin 54(1), 99-102, 2006-01-01
… The purpose of this study is to assess the suitability of spray dried excipient base in the formulation of ODTs of Valdecoxib (low aqueous solubility) and Metoclopramide (high aqueous solubility). …
NAID 110004820332

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Valdecoxib
Systematic (IUPAC) name
	4-(5-methyl-3-phenylisoxazol-4-yl)benzenesulfonamide
Clinical data
Pregnancy cat.	C (AU) May cause premature closure of the ductus arteriosus
Legal status	Withdrawn in U.S., EU, Canada & parts of Asia
Routes	Oral
Pharmacokinetic data
Bioavailability	83%
Protein binding	98%
Metabolism	Hepatic (CYP3A4 and 2C9 involved)
Half-life	8 to 11 hours
Excretion	Renal
Identifiers
CAS number	181695-72-7
ATC code	M01AH03
PubChem	CID 119607
DrugBank	DB00580
ChemSpider	106796
UNII	2919279Q3W
KEGG	D02709
ChEMBL	CHEMBL865
Chemical data
Formula	C16H14N2O3S
Mol. mass	314.364 g/mol
	SMILES O=S(=O)(N)c3ccc(c2c(onc2c1ccccc1)C)cc3;
	InChI InChI=1S/C16H14N2O3S/c1-11-15(12-7-9-14(10-8-12)22(17,19)20)16(18-21-11)13-5-3-2-4-6-13/h2-10H,1H3,(H2,17,19,20) ; Key:LNPDTQAFDNKSHK-UHFFFAOYSA-N ;
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英: valdecoxib
同: Bextra(Pfizer)
関: 非ステロイド性抗炎症薬

[0] Thomson Micromedex. "Valdecoxib. U.S. FDA Drug Approval." Last accessed June 8, 2007.

[Off-label-1] "Pfizer to pay $2.3 billion to resolve criminal and civil health care liability relating to fraudulent marketing and the payment of kickbacks". Stop Medicare Fraud, US Dept of Health & Human Svc, and of Justice. http://www.stopmedicarefraud.gov/pfizerfactsheet.html. Retrieved 2012-07-04.

[2] "Adverse Effects of Cyclooxygenase-2 Inhibitors on Renal and Arrhythmia Events: Meta-Analysis of Randomized Trials", (JAMA 2006, by Zhang JJ, Ding EL, Song Y.).

[3] ttp://news.bbc.co.uk/2/hi/business/8234533.stm Pfizer agrees record fraud fine

[4] ttp://www.usdoj.gov/usao/ma/Press%20Office%20-%20Press%20Release%20Files/Sept2009/PharmaciaPlea.html

[5] ttp://www.usdoj.gov/usao/ma/Press%20Office%20-%20Press%20Release%20Files/Mar2009/FarinaconvictionPR.html

[6] ttp://industry.bnet.com/pharma/10002882/pfizers-off-label-bextra-team-were-called-the-highlanders/

[7] ttp://www.usdoj.gov/usao/ma/Press%20Office%20-%20Press%20Release%20Files/June2009/HollowayMarySentencingPR.html

[8] ttp://www.fbi.gov/pressrel/pressrel09/justice_090209.htm

[9] ttp://www.phillipsandcohen.com/CM/NewsSettlements/NewsSettlements536.asp

[10] ttp://www.phillipsandcohen.com/CM/NewsSettlements/NewsSettlements531.asp

[11] Talley, J. J.; Brown, D. L.; Carter, J. S.; Graneto, M. J.; Koboldt, C. M.; Masferrer, J. L.; Perkins, W. E.; Rogers, R. S. et al. (2000). "4-[5-Methyl-3-phenylisoxazol-4-yl]- benzenesulfonamide, Valdecoxib: A Potent and Selective Inhibitor of COX-2". Journal of Medicinal Chemistry 43 (5): 775. doi:10.1021/jm990577v. PMID 10715145. edit

[12] Prafulla Kumar Sahu and M. Mathrusri Annapurna, Analytical method development by liquid chromatography, LAP Lambert Academic Publisher, Germany, 2011 ISBN 3-8443-2869-6.

[13] Zhang J Y, Fast D M and Breau A P, J Chromatogr B Analyt Technol Biomed Life Sci., 2003, 785(1), 123-134

[14] Ramakrishna N V S, Vishwottam K N; Wishu S and Koteshwara M, J Chromatogr B Analyt Technol Biomed Life Sci., 2004, 802(2), 271.

[15] Sane R T, Menon S, Deshpande A Y and Jain A, Chromatogr., 2005, 61(3-4), 137-141.

[16] Prafulla Kumar Sahu*, K. Ravi Sankar and M. Mathrusri Annapurna, Determination of Valdecoxib in human plasma using Reverse Phase HPLC”, E-Journal of Chemistry, 2011, 8(2), 875-881.

[17] Mandal U, Jayakumar M, Ganesan M, Nandi S, Pal T K, Chakraborty M K, Roy Chowdhary A. and Chattoraj T K, Indian Drugs, 2004, 41, 59.

[18] Zhang J.Y, Fast D.M and Breau, A.P, J Pharm Biomed Anal., 2003, 33, 61.

[19] Werner U, Werner D, Hinz B, Lanbrecht C and Brune K, J Biomed Chromatogr., 2004, 19, 113.

[20] Zhang J V, Fast D M and Breau A P, J Chromatogr B Anal Technol Biomed Life Sci., 2003, 785, 123.

[21] Sutariya V B, Rajashree M, Sankalia M G. and Priti P, Indian J Pharm Sci., 2004, 93, 112.

[22] Gandhimathi M, Ravi T K, Shukla Nilima and Sowmiya G, Indian J Pharm Sci., 2007, 69(1), 145-147.

匿名

検索

案内

案内

valdecoxib

WordNet

Wikipedia preview

wiki en

Contents

Uses until 2005

Side-effects and withdrawal from market

2009 settlement for off-label uses promotions

Synthesis

Assay of Valdecoxib^[13]

See also

References

External links

UpToDate Contents

English Journal

Japanese Journal

Related Links

Related Pictures

★リンクテーブル★

「バルデコキシブ」

匿名

検索

案内

valdecoxib

WordNet

Wikipedia preview

wiki en

Contents

Uses until 2005

Side-effects and withdrawal from market

2009 settlement for off-label uses promotions

Synthesis

Assay of Valdecoxib[13]

See also

References

External links

UpToDate Contents

English Journal

Japanese Journal

Related Links

Related Pictures

★リンクテーブル★

「バルデコキシブ」

Assay of Valdecoxib^[13]