Benzbromarone Explained

Benzbromarone 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 in April 2008 have suggested it is superior to both allopurinol, a non-uricosuric xanthine oxidase inhibitor, and probenecid, another uricosuric drug.[7] [8]

Mechanism of action

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]

History

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In 2003, the drug was withdrawn by Sanofi-Synthélabo, after reports of serious hepatotoxicity, although it is still marketed in several countries by other drug companies.[12]

Notes and References

  1. Sinclair DS, Fox IH . The pharmacology of hypouricemic effect of benzbromarone . The Journal of Rheumatology . 2 . 4 . 437–45 . December 1975 . 1206675 .
  2. Kumar V, Locuson CW, Sham YY, Tracy TS . Amiodarone analog-dependent effects on CYP2C9-mediated metabolism and kinetic profiles . Drug Metabolism and Disposition . 34 . 10 . 1688–96 . October 2006 . 16815961 . 10.1124/dmd.106.010678 .
  3. Heel RC, Brogden RN, Speight TM, Avery GS . 8198915 . Benzbromarone: a review of its pharmacological properties and therapeutic use in gout and hyperuricaemia . Drugs . 14 . 5 . 349–66 . November 1977 . 338280 . 10.2165/00003495-197714050-00002 .
  4. Masbernard A, Giudicelli CP . Ten years' experience with benzbromarone in the management of gout and hyperuricaemia . South African Medical Journal = Suid-Afrikaanse Tydskrif vir Geneeskunde . 59 . 20 . 701–6 . May 1981 . 7221794 .
  5. Perez-Ruiz F, Alonso-Ruiz A, Calabozo M, Herrero-Beites A, García-Erauskin G, Ruiz-Lucea E . 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 . September 1998 . 9849314 . 1752740 . 10.1136/ard.57.9.545 .
  6. Reinders MK, van Roon EN, Houtman PM, Brouwers JR, Jansen TL . Biochemical effectiveness of allopurinol and allopurinol-probenecid in previously benzbromarone-treated gout patients . Clinical Rheumatology . 26 . 9 . 1459–65 . September 2007 . 17308859 . 10.1007/s10067-006-0528-3 . free .
  7. Schepers GW . 33337546 . Benzbromarone therapy in hyperuricaemia; comparison with allopurinol and probenecid . The Journal of International Medical Research . 9 . 6 . 511–5 . 1981 . 7033016 . 10.1177/030006058100900615 .
  8. Reinders MK, van Roon EN, Jansen TL, Delsing J, Griep EN, Hoekstra M, van de Laar MA, Brouwers JR . 6 . 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 . January 2009 . 18250112 . 10.1136/ard.2007.083071 .
  9. Hummel MA, Locuson CW, Gannett PM, Rock DA, Mosher CM, Rettie AE, Tracy TS . 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 . 3 . 644–51 . September 2005 . 15955872 . 1552103 . 10.1124/mol.105.013763 .
  10. Locuson CW, Rock DA, Jones JP . Quantitative binding models for CYP2C9 based on benzbromarone analogues . Biochemistry . 43 . 22 . 6948–58 . June 2004 . 15170332 . 10.1021/bi049651o . 10.1.1.127.2015 .
  11. Locuson CW, Suzuki H, Rettie AE, Jones JP . Charge and substituent effects on affinity and metabolism of benzbromarone-based CYP2C19 inhibitors . Journal of Medicinal Chemistry . 47 . 27 . 6768–76 . December 2004 . 15615526 . 10.1021/jm049605m .
  12. Lee MH, Graham GG, Williams KM, Day RO . 1204662 . A benefit-risk assessment of benzbromarone in the treatment of gout. Was its withdrawal from the market in the best interest of patients? . Drug Safety . 31 . 8 . 643–65 . 2008 . 18636784 . 10.2165/00002018-200831080-00002 .

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Benzbromarone".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.