Benzbromarone

Benzbromarone
Systematic (IUPAC) name
(3,5-dibromo-4-hydroxyphenyl)-(2-ethyl-1-benzofuran-3-yl)methanone
Clinical data
AHFS/Drugs.com International Drug Names
Identifiers
CAS Number 3562-84-3 N
ATC code M04AB03 (WHO)
PubChem CID 2333
ChemSpider 2243 YesY
UNII 4POG0RL69O YesY
ChEBI CHEBI:3023 YesY
ChEMBL CHEMBL388590 YesY
Chemical data
Formula C17H12Br2O3
Molar mass 424.083 g/mol
Physical data
Melting point 161 to 163 °C (322 to 325 °F)
 NYesY (what is this?)  (verify)

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In 2003, the drug was withdrawn by Sanofi-Synthélabo, after reports of serious hepatotoxicity, although it is still marketed in several countries by other drug companies.[12]

See also

References

  1. ↑ Sinclair, DS; Fox, IH (1975). "The pharmacology of hypouricemic effect of benzbromarone". The Journal of rheumatology 2 (4): 437–45. PMID 1206675.
  2. 1 2 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.
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ Schepers, GW (1981). "Benzbromarone therapy in hyperuricaemia; comparison with allopurinol and probenecid". The Journal of International Medical Research 9 (6): 511–5. PMID 7033016.
  8. ↑ 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.
  9. ↑ 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 68: 644–51. doi:10.1124/mol.105.013763. PMC 1552103. PMID 15955872.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
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