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Benzbromarone (INN) is a uricosuric agent and non-competitive inhibitor of xanthine oxidase^[1] used in the treatment of gout, especially when allopurinol, a first-line treatment, fails or produces intolerable adverse effects. It is structurally related to the antiarrhythmic amiodarone.^[2]

Benzbromarone is highly effective and well tolerated,^[3]^[4]^[5]^[6] and clinical trials as early as 1981 and as recently as April 2008 have suggested it is superior to both allopurinol, a xanthine oxidase inhibitor but not uricosuric, and probenecid, another uricosuric drug.^[7]^[8]

Effect on cytochrome P450

Benzbromarone is a very potent inhibitor of CYP2C9.^[2]^[9] Several analogues of the drug have been developed as CYP2C9 and CYP2C19 inhibitors for use in research.^[10]^[11]

Safety

Benzbromarone was introduced in the 1970s and was viewed as having few associated serious adverse reactions. It was registered in about 20 countries throughout Europe, Asia and South America.

In 2003, the drug was withdrawn by Sanofi-Synthélabo, after reports of serious hepatotoxicity, although it is still marketed in several countries by other drug companies.^[12]

References

^ Sinclair, DS; Fox, IH (1975). "The pharmacology of hypouricemic effect of benzbromarone". The Journal of rheumatology 2 (4): 437–45. PMID 1206675.
^ ^a ^b Kumar, V.; Locuson, CW; Sham, YY; Tracy, TS (2006). "Amiodarone Analog-Dependent Effects on CYP2C9-Mediated Metabolism and Kinetic Profiles". Drug Metabolism and Disposition 34 (10): 1688–96. doi:10.1124/dmd.106.010678. PMID 16815961.
^ Heel, R.C.; Brogden, R.N.; Speight, T.M.; Avery, G.S. (1977). "Benzbromarone". Drugs 14 (5): 349–66. doi:10.2165/00003495-197714050-00002. PMID 338280.
^ Masbernard, A; Giudicelli, CP (1981). "Ten years' experience with benzbromarone in the management of gout and hyperuricaemia" (PDF). South African Medical Journal 59 (20): 701–6. PMID 7221794.
^ Perez-Ruiz, F; Alonso-Ruiz, A; Calabozo, M; Herrero-Beites, A; Garcia-Erauskin, G; Ruiz-Lucea, E (1998). "Efficacy of allopurinol and benzbromarone for the control of hyperuricaemia. A pathogenic approach to the treatment of primary chronic gout". Annals of the Rheumatic Diseases 57 (9): 545–9. doi:10.1136/ard.57.9.545. PMC 1752740. PMID 9849314.
^ Reinders, Mattheus K.; Roon, Eric N.; Houtman, Pieternella M.; Brouwers, Jacobus R. B. J.; Jansen, Tim L. Th. A. (2007). "Biochemical effectiveness of allopurinol and allopurinol-probenecid in previously benzbromarone-treated gout patients". Clinical Rheumatology 26 (9): 1459–65. doi:10.1007/s10067-006-0528-3. PMID 17308859.
^ Schepers, GW (1981). "Benzbromarone therapy in hyperuricaemia; comparison with allopurinol and probenecid". The Journal of International Medical Research 9 (6): 511–5. PMID 7033016.
^ Reinders, M K; Van Roon, E N; Jansen, T L T. A; Delsing, J; Griep, E N; Hoekstra, M; Van De Laar, M A F J; Brouwers, J R B J (2008). "Efficacy and tolerability of urate-lowering drugs in gout: A randomised controlled trial of benzbromarone versus probenecid after failure of allopurinol". Annals of the Rheumatic Diseases 68 (1): 51–6. doi:10.1136/ard.2007.083071. PMID 18250112.
^ Hummel, M. A. (2005). "CYP2C9 Genotype-Dependent Effects on in Vitro Drug-Drug Interactions: Switching of Benzbromarone Effect from Inhibition to Activation in the CYP2C9.3 Variant". Molecular Pharmacology. doi:10.1124/mol.105.013763.
^ Locuson, Charles W.; Rock, Denise A.; Jones, Jeffrey P. (2004). "Quantitative Binding Models for CYP2C9 Based on Benzbromarone Analogues†". Biochemistry 43 (22): 6948–58. doi:10.1021/bi049651o. PMID 15170332.
^ Locuson, Charles W.; Suzuki, Hisashi; Rettie, Allan E.; Jones, Jeffrey P. (2004). "Charge and Substituent Effects on Affinity and Metabolism of Benzbromarone-Based CYP2C19 Inhibitors". Journal of Medicinal Chemistry 47 (27): 6768–76. doi:10.1021/jm049605m. PMID 15615526.
^ Lee, Ming-Han H; Graham, Garry G; Williams, Kenneth M; Day, Richard O (2008). "A Benefit-Risk Assessment of Benzbromarone in the Treatment of Gout". Drug Safety 31 (8): 643–65. doi:10.2165/00002018-200831080-00002. PMID 18636784.

UpToDate Contents

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1. 腎移植レシピエントにおける高尿酸血症および痛風 hyperuricemia and gout in renal transplant recipients
2. 痛風再発の予防 prevention of recurrent gout
3. 急性痛風の治療 treatment of acute gout
4. 低尿酸血症：原因および臨床的意義 hypouricemia causes and clinical significance
5. 常染色体優性間質性腎臓病（髄質嚢胞性腎疾患） autosomal dominant interstitial kidney disease medullary cystic kidney disease

English Journal

[Treatment of gout].

Dubost JJ, Mathieu S, Soubrier M.SourceService de rhumatologie, hôpital G. Montpied, CHU, BP 69, 63003 Clermont-Ferrand cedex 1, France.
La Revue de médecine interne / fondée ... par la Société nationale francaise de médecine interne.Rev Med Interne.2011 Dec;32(12):751-7. Epub 2011 Mar 5.
In France, colchicine remains the standard treatment for the acute flare of gout. The lowest dose currently used decreases digestive toxicity. Doses of colchicine should be adapted to renal function and age, and possible drug interactions should be considered. Non steroidal anti-inflammatory drugs a
PMID 21382654

Use of Uric Acid-Lowering Agents Limits Experimental Cyclosporine Nephropathy.

Mazali FC, Johnson RJ, Mazzali M.SourceDivision of Nephrology, School of Medical Sciences, State University of Campinas, UNICAMP, Campinas, Brazil.
Nephron. Experimental nephrology.Nephron Exp Nephrol.2011 Nov 25;120(1):e12-e19. [Epub ahead of print]
Background: Hyperuricemia frequently complicates cyclosporine (CsA) therapy. Previous studies have shown that hyperuricemia exacerbates interstitial and vascular lesions in the cyclosporine model. We tested the hypothesis that normalization of uric acid could prevent the development of cyclosporine
PMID 22126908

Japanese Journal

ジェネリック医薬品"ベンズブロマロン錠"の高尿酸血症患者の腎機能に及ぼす影響 : 年齢と投与量による変化

寺岡大輔,杉山恵理,蘆田孝,長友孝文,宮尾益尚
応用薬理 82(3), 35-38, 2012-06-08
NAID 10030595076

痛風患者におけるbenzbromarone投与のCRPに対する影響

角田千尋,蔵城雅文,庄司拓仁,小山英則,堤善多,森脇優司,山本徹也
痛風と核酸代謝 36(1), 60, 2012
NAID 130001922016

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★リンクテーブル★

リンク元	「薬理学」「ベンズブロマロン」「痛風治療薬」

「薬理学」

Benzbromarone
Systematic (IUPAC) name
	(3,5-dibromo-4-hydroxyphenyl)- (2-ethyl-3-benzofuranyl)methanone
Clinical data
AHFS/Drugs.com	International Drug Names
Identifiers
CAS Registry Number	3562-84-3
ATC code	M04AB03
PubChem	CID 2333
ChemSpider	2243
UNII	4POG0RL69O
ChEBI	CHEBI:3023
ChEMBL	CHEMBL388590
Chemical data
Formula	C17H12Br2O3
Molecular mass	424.083 g/mol
	SMILES Brc1cc(cc(Br)c1O)C(=O)c2c3ccccc3oc2CC;
	InChI InChI=1S/C17H12Br2O3/c1-2-13-15(10-5-3-4-6-14(10)22-13)16(20)9-7-11(18)17(21)12(19)8-9/h3-8,21H,2H2,1H3 ; Key:WHQCHUCQKNIQEC-UHFFFAOYSA-N ;
Physical data
Melting point	161 to 163 °C (322 to 325 °F)
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英: pharmacology
関: drug entries

定義

生物系と化学物質の選択的な相互作用を研究する学問 (SPC.2)

生物系と薬の相互作用

薬の生物系に対する相互作用：薬理作用 <-化学の視点
生物系の薬に対する相互作用：薬物動態 <-生物の視点

薬品の命名

Ending of the drug name	Category	Example
～afil	Erectile dysfunction	sildenafil
～ane	Inhalatinal general anesthetic	halothane
～azepam	Benzodiaizepine	diazepam
～azine	Phenothiazine (neuroleptic, antiemetic)	chlorpromazine
～azole	Ailtifungal	ketoconazole
～barbital	Barbiturate	phenobarbital
～caine	Local anesthetic	lidocaine
～cillin	Penicillin	methicillin
～cycline	Antibiotic, protein syntlesis inhibitor	tetracycline
～ipramine	TCA	iimipramine
～navir	Protease inhibitor	saquinavir
～olol	β-antagonist	propranolol
～operidol	Butyrophenone ( neuroleptic )	haloperidol
～oxin	Cardiac glycoside ( inotropic agent )	digoxin
～phylline	Methylxanthine	theophylline
～pril	ACE inhibitor	captopril
～terol	β₂ agonist	albuterol
～tidine	H₂ antagonist	cimtidine
～triptyline	TCA	amitriptyline
～tropine	Pituitary hormone	somatotropine
～zosin	a₁ antagonist	prazosin