Crystal deposition disorders
Ashley W. Blom, David Warwick, Michael R. Whitehouse in Apley and Solomon’s System of Orthopaedics and Trauma, 2017
Other ULT agents are ‘uricosuric’, increasing excretion of urate at the kidney. In general they are less effective than allopurinol and are contraindicated in urolithiasis. Examples include probenecid and sulphinpyrazone, which act by inhibiting URAT1. Benzbromarone is an effective uricosuric but is not widely available.
B
Caroline Ashley, Aileen Dunleavy, John Cunningham in The Renal Drug Handbook, 2018
Biological effect of 100 mg benzbromarone is equivalent to 1.5 g probenecid or greater than 300 mg of allopurinol. (Masbernard A. Ten years’ experience with benzbromarone in the management of gout and hyperuricaemia. SAMJ. 1981; 59(20): 701–6.)
Advances in pharmacotherapies for hyperuricemia
Published in Expert Opinion on Pharmacotherapy, 2023
Federica Piani, Davide Agnoletti, Claudio Borghi
Benzbromarone has been the most widely used uricosuric drug for the treatment of gout. Currently, it is available only in Germany, The Netherlands, and Spain due to concerns around its hepatotoxicity [60]. Benzbromarone acts inhibiting URAT1 and GLUT9, the latter possibly being involved in both the reabsorption and the secretion of uric acid in the proximal tubule [59]. Its use is only approved in monotherapy, except for Germany that allows the combination with XO inhibitors. The usual dosage goes from 50 to 100 mg once/daily, the peak concentration is reached within 2 h and the half-life goes from 4 to 17 h [32]. Due to its potential hepatotoxicity, it is recommended to check serum transaminases every 3 months [60]. A common side effect is diarrhea and caution is needed for concomitant treatments with CYP2C9-metabolized drugs such as warfarin. Finally, although mainly metabolized by the liver, benzbromarone should not be administered in severe kidney failure (eGFR<20 ml/min).
Safety and efficacy of verinurad, a selective URAT1 inhibitor, for the treatment of patients with gout and/or asymptomatic hyperuricemia in the United States and Japan: Findings from two phase II trials
Published in Modern Rheumatology, 2019
David Fitz-Patrick, Kent Roberson, Kiyoshi Niwa, Takabumi Fujimura, Koji Mori, Jesse Hall, Xiaohong Yan, Zancong Shen, Sha Liu, Yasushi Ito, Scott Baumgartner
It may be instructive to consider the similarities and differences between verinurad and benzbromarone, another URAT1 inhibitor. Benzbromarone is used as first-line treatment of hyperuricemia in Japanese patients with gout who under-excrete uric acid [7,8]. Its use is generally considered to not be associated with renal AEs, although no large well-controlled studies with frequent sCR monitoring are available. When benzbromarone and verinurad were compared in a head-to-head study, benzbromarone demonstrated a lower maximum rate of uric acid excretion compared with verinurad [24]. This is important because we believe that the maximal rate of uric acid excretion correlates with risk for a renal AE, as too much uric acid in the renal tubule at one time leads to saturation and precipitation of uric acid (uric acid nephropathy). The lower rate with benzbromarone likely allows it to be safely dosed as monotherapy. Benzbromarone also has prolonged urate-lowering activity because it has an active metabolite with a long half-life [28]. The long duration of action enables a steady urinary excretion of uric acid, which prevents the uric acid from precipitating. A patient on benzbromarone excretes uric acid at a lower steady rate over the entire 24-hour period post dosing whereas a patient on verinurad excretes uric acid at a higher rate over the initial 6–8 hours. The higher rate of excretion with verinurad was reduced to less than or equal to that with benzbromarone when combined with an XOI [24].
Lycium barbarum polysaccharides protect mice from hyperuricaemia through promoting kidney excretion of uric acid and inhibiting liver xanthine oxidase
Published in Pharmaceutical Biology, 2020
Xin Yu, Lu Zhang, Ping Zhang, Jia Zhi, Ruinan Xing, Lianqi He
To test the hypothesis above, we assessed the mRNA expression levels of Slc22a6, Slc22a8 and Slc2a9 in the kidneys of each mouse group. The results showed that LBPs upregulated the expression levels of Slc22a6 and Slc22a8 but downregulated those of Slc2a9 in the hyperuricemic mouse kidney. At the protein level, LBPs increased the expression levels of OAT1 and OAT3 and decreased the expression level of GLUT9 in the hyperuricemic mouse kidney. These results indicated that LBPs reduce the level of uric acid in the blood by increasing the excretion of uric acid and reducing the reabsorption of uric acid by the kidney. The clinical first-line anti-hyperuricaemia drug benzbromarone works by strengthening the excretion of uric acid in the kidney’s proximal tubule, thereby maintaining blood uric acid at a suitable level. However, many studies have demonstrated the hepatotoxicity of benzbromarone (Wang et al. 2016, 2017), which restricted its usage in some countries, such as the United States.