Benzbromarone in the treatment of gout

被引:151
作者
Azevedo, Valderilio Feijo [1 ,2 ]
Kos, Igor Age [2 ]
Vargas-Santos, Ana Beatriz [3 ]
Castelar Pinheiro, Geraldo da Rocha [3 ]
Paiva, Eduardo dos Santos [1 ]
机构
[1] Univ Fed Parana, Rua Gen Carneiro 181, Curitiba, Parana, Brazil
[2] Edumed Educ Saude, Rua Bispo Dom Jose 2495, Curitiba, Parana, Brazil
[3] Univ Estado Rio De Janeiro, Rio De Janeiro, Brazil
关键词
EPOXIDE-DERIVED METABOLITE(S); URATE-LOWERING THERAPY; CHRONIC KIDNEY-DISEASE; PEROXISOME PROLIFERATION; URIC-ACID; EFFICACY; HYPERURICEMIA; FAILURE; SAFETY; ALLOPURINOL;
D O I
10.1186/s42358-019-0080-x
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
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. Main body of the abstract 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 Due to hepatotoxicity reports, it was withdrawn from the European market by the manufacturer, however many authors have questioned the product's withdrawal due to a lack of clinical evidence in order to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.
引用
收藏
页数:5
相关论文
共 53 条
[11]
DEVRIES JX, 1993, CLIN INVESTIGATOR, V71, P947
[12]
Molecular identification of a renal urate-anion exchanger that regulates blood urate levels [J].
Enomoto, A ;
Kimura, H ;
Chairoungdua, A ;
Shigeta, Y ;
Jutabha, P ;
Cha, SH ;
Hosoyamada, M ;
Takeda, M ;
Sekine, T ;
Igarashi, T ;
Matsuo, H ;
Kikuchi, Y ;
Oda, T ;
Ichida, K ;
Hosoya, T ;
Shimokata, K ;
Niwa, T ;
Kanai, Y ;
Endou, H .
NATURE, 2002, 417 (6887) :447-452
[13]
Hepatocellular toxicity of benzbromarone: Effects on mitochondrial function and structure [J].
Felser, Andrea ;
Lindinger, Peter W. ;
Schnell, Dominik ;
Kratschmar, Denise V. ;
Odermatt, Alex ;
Mies, Suzette ;
Jenoe, Paul ;
Kraehenbuehl, Stephan .
TOXICOLOGY, 2014, 324 :136-146
[14]
Hyperuricaemia, chronic kidney disease, and outcomes in heart failure: potential mechanistic insights from epidemiological data [J].
Filippatos, Gerasimos S. ;
Ahmed, Mustafa I. ;
Gladden, James D. ;
Mujib, Marjan ;
Aban, Inmaculada B. ;
Love, Thomas E. ;
Sanders, Paul W. ;
Pitt, Bertram ;
Anker, Stefan D. ;
Ahmed, Ali .
EUROPEAN HEART JOURNAL, 2011, 32 (06) :712-720
[15]
Fornasier G, 2018, INT J CLIN PHARM, P21
[16]
Hanvivadhanakul Punchong, 2002, Journal of the Medical Association of Thailand, V85, pS40
[17]
EFFECT OF SINGLE ORAL DOSES OF BENZBROMARONE ON SERUM AND URINARY URIC-ACID [J].
JAIN, AK ;
RYAN, JR ;
MCMAHON, FG ;
NOVECK, RJ .
ARTHRITIS AND RHEUMATISM, 1974, 17 (02) :149-157
[18]
Mechanisms of benzarone and benzbromarone-induced hepatic toxicity [J].
Kaufmann, P ;
Török, M ;
Hänni, A ;
Roberts, P ;
Gasser, R ;
Krähenbühl, S .
HEPATOLOGY, 2005, 41 (04) :925-935
[19]
Novel Bioactivation Pathway of Benzbromarone Mediated by Cytochrome P450 [J].
Kitagawara, Yumina ;
Ohe, Tomoyuki ;
Tachibana, Kumiko ;
Takahashi, Kyoko ;
Nakamura, Shigeo ;
Mashino, Tadahiko .
DRUG METABOLISM AND DISPOSITION, 2015, 43 (09) :1303-1306
[20]
Cytotoxic Effects of Benzbromarone and Its 1′-Hydroxy Metabolite in Human Hepatocarcinoma FLC4 Cells Cultured on Micro-space Cell Culture Plates [J].
Kobayashi, Kaoru ;
Kajiwara, Eri ;
Ishikawa, Masayuki ;
Mimura, Hanaka ;
Oka, Hidenobu ;
Ejiri, Yoko ;
Hosoda, Masaya ;
Chiba, Kan .
DRUG METABOLISM AND PHARMACOKINETICS, 2013, 28 (03) :265-268