RESUMO
BACKGROUND: Benzbromarone is a uricosuric drug that has been used in the treatment of gout over the last 30 years. Due to its potent inhibition of the dominant apical (luminal) urate exchanger in the human proximal tubule URAT1, it reduces the urate reabsorption, diminishing serum urate levels and therefore preventing gout flares. Through several clinical trials, Benzbromarone has been proved effective and safe, inclusive in patients with chronic kidney disease and as combination therapy with allopurinol. Due to hepatotoxicity reports, it was withdrawn from the European market by the manufacturer, however many authors have questioned the product's withdrawal due to a lack of clinical evidence in order to support its hepatotoxicity. Benzbromarone is still available in several European countries, New Zealand, Brazil and several other countries. Despite the product's marketing over more than 20 years after the first hepatotoxicity reports, we have found only five reports in our literature search, and no prospective or retrospective study correlating hepatotoxicity with benzbromarone use. SHORT CONCLUSION: Benzbromarone is a safe and effective molecule for the treatment of gout. However, due to in vitro and in vivo data related to hepatotoxicity, it is prudent to prescribe it with some caution, especially for patients with an already known liver condition.
Assuntos
Benzobromarona/uso terapêutico , Gota/tratamento farmacológico , Uricosúricos/uso terapêutico , Benzobromarona/efeitos adversos , Benzobromarona/metabolismo , Citocromo P-450 CYP2C9/metabolismo , Humanos , Técnicas In Vitro , Fígado/efeitos dos fármacos , Fígado/metabolismo , Mitocôndrias Hepáticas/efeitos dos fármacos , Modelos Animais , Transportadores de Ânions Orgânicos/antagonistas & inibidores , Proteínas de Transporte de Cátions Orgânicos/antagonistas & inibidores , Retirada de Medicamento Baseada em Segurança , Exacerbação dos Sintomas , Uricosúricos/efeitos adversos , Uricosúricos/metabolismoRESUMO
Uricosuric diuretics have been developed to counteract renal urate retention accompanying diuretic-induced extracellular volume contraction. Their intrinsic uricosuric activity would prevent diuretic-induced hyperuricemia. Ticrynafen, a prototype uricosuric diuretic, has largely fallen into disuse because of hepatic toxicity. However, one lesson learned during the short period that ticrynafen was available in the US is that the administration of a potent uricosuric agent to a patient previously trated with diuretics can precipitate acute renal failure, possibly as a consequence of uric acid nephropathy. Another novel uricosuric diuretic, indacrinone, is composed of two enantiomorphic isomers exhibiting predominantly either a uricosuric or a natriuretic action. Manipulation of the isomer ratio currently is being attempted with a view toward obtaining a combination that produces little change in the serum urate during chronic diuretic therapy. Uricosuric diuretics have the therapeutic potential to treat hypertension and edematous states without increasing the serum urate. Although current information suggests that chronic asymptomatic hyperuricemia poses very little health hazard, future data could indicate that it may be desirable to maintain the serum urate near the normal range