Benzbromarone
Benzbromarone (INN) is a uricosuric agent 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.[1]
Benzbromarone is highly effective and well-tolerated,[2][3][4][5] and clinical trials as early as 1981 and as recently as April 2008 have suggested it is superior to both allopurinol and probenecid, another uricosuric drug.[6][7]
Effect on cytochrome P450
Benzbromarone is a very potent inhibitor of CYP2C9.[1][8] Several analogues of the drug have been developed as CYP2C9 and CYP2C19 inhibitors for use in research.[9][10]
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In 2003, the drug was withdrawn by Sanofi-Synthélabo, after reports of serious hepatotoxicity, although it is still marketed in several countries by other drug companies. [11]
See also
References
- ^ a b Kumar V, Locuson CW, Sham YY, Tracy TS (October 2006). "Amiodarone analog-dependent effects on CYP2C9-mediated metabolism and kinetic profiles". Drug Metab. Dispos. 34 (10): 1688–96. doi:10.1124/dmd.106.010678. PMID 16815961.
- ^ Heel RC, Brogden RN, Speight TM, Avery GS (November 1977). "Benzbromarone: a review of its pharmacological properties and therapeutic use in gout and hyperuricaemia". Drugs 14 (5): 349–66. PMID 338280.
- ^ Masbernard A, Giudicelli CP (May 1981). "Ten years' experience with benzbromarone in the management of gout and hyperuricaemia". S. Afr. Med. J. 59 (20): 701–6. PMID 7221794.
- ^ Perez-Ruiz F, Alonso-Ruiz A, Calabozo M, Herrero-Beites A, García-Erauskin G, Ruiz-Lucea E (September 1998). "Efficacy of allopurinol and benzbromarone for the control of hyperuricaemia. A pathogenic approach to the treatment of primary chronic gout". Ann. Rheum. Dis. 57 (9): 545–9. doi:10.1136/ard.57.9.545. PMC 1752740. PMID 9849314. http://ard.bmj.com/cgi/pmidlookup?view=long&pmid=9849314.
- ^ Reinders MK, van Roon EN, Houtman PM, Brouwers JR, Jansen TL (September 2007). "Biochemical effectiveness of allopurinol and allopurinol-probenecid in previously benzbromarone-treated gout patients". Clin. Rheumatol. 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". J. Int. Med. Res. 9 (6): 511–5. PMID 7033016.
- ^ Reinders MK, van Roon EN, Jansen TL et al. (April 2008). "Efficacy and tolerability of urate lowering drugs in gout: a randomised controlled trial of benzbromarone versus probenecid after failure of allopurinol". Ann. Rheum. Dis. 68 (1): 51–6. doi:10.1136/ard.2007.083071. PMID 18250112.
- ^ Hummel MA, Locuson CW, Gannett PM et al. (September 2005). "CYP2C9 Genotype-Dependent Effects on In Vitro Drug-Drug Interactions: Switching of Benzbromarone Effect from Inhibition to Activation in the CYP2C9.3 Variant". Mol. Pharmacol. 68 (3): 644–51. doi:10.1124/mol.105.013763. PMC 1552103. PMID 15955872. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1552103.
- ^ Locuson CW, Rock DA, Jones JP (June 2004). "Quantitative binding models for CYP2C9 based on benzbromarone analogues". Biochemistry 43 (22): 6948–58. doi:10.1021/bi049651o. PMID 15170332.
- ^ Locuson CW, Suzuki H, Rettie AE, Jones JP (December 2004). "Charge and substituent effects on affinity and metabolism of benzbromarone-based CYP2C19 inhibitors". J. Med. Chem. 47 (27): 6768–76. doi:10.1021/jm049605m. PMID 15615526.
- ^ Lee MH, Graham GG, Williams KM, Day RO (2008). "A benefit-risk assessment of benzbromarone in the treatment of gout. Was its withdrawal from the market in the best interest of patients?". Drug Saf 31 (8): 643–65. PMID 18636784.