uricosuric agents


Summary: Gout suppressants that act directly on the renal tubule to increase the excretion of uric acid, thus reducing its concentrations in plasma.

Top Publications

  1. Ichida K, Hosoyamada M, Kimura H, Takeda M, Utsunomiya Y, Hosoya T, et al. Urate transport via human PAH transporter hOAT1 and its gene structure. Kidney Int. 2003;63:143-55 pubmed
    ..Our data show that hOAT1 transports urate, and the inhibition profiles of uricosuric and antiuricosuric agents are defined. hOAT1 is not responsible for FJGN in the two sisters examined in this study. ..
  2. Fam A. Difficult gout and new approaches for control of hyperuricemia in the allopurinol-allergic patient. Curr Rheumatol Rep. 2001;3:29-35 pubmed
    ..The management of gout in these patients is complicated by two main factors: cyclosporine-induced renal impairment, and interactions with medications used to preserve the allograft. ..
  3. Reinders M, Haagsma C, Jansen T, van Roon E, Delsing J, van de Laar M, et al. A randomised controlled trial on the efficacy and tolerability with dose escalation of allopurinol 300-600 mg/day versus benzbromarone 100-200 mg/day in patients with gout. Ann Rheum Dis. 2009;68:892-7 pubmed publisher
    ..30 mmol/l). No significant differences in treatment success between benzbromarone and allopurinol were found after dose escalation. ISRCTN49563848). ..
  4. George J, Carr E, Davies J, Belch J, Struthers A. High-dose allopurinol improves endothelial function by profoundly reducing vascular oxidative stress and not by lowering uric acid. Circulation. 2006;114:2508-16 pubmed
    ..The reduction in vascular oxidative stress was profound because high-dose allopurinol totally abolished the oxidative stress that was sensitive to the high-dose vitamin C that was used in this study. ..
  5. Nzila A, Mberu E, Bray P, Kokwaro G, Winstanley P, Marsh K, et al. Chemosensitization of Plasmodium falciparum by probenecid in vitro. Antimicrob Agents Chemother. 2003;47:2108-12 pubmed
    ..P. Thompson & Co., Liverpool, United Kingdom] has been filed to protect this intellectual property). ..
  6. Shin H, Takeda M, Enomoto A, Fujimura M, Miyazaki H, Anzai N, et al. Interactions of urate transporter URAT1 in human kidney with uricosuric drugs. Nephrology (Carlton). 2011;16:156-62 pubmed publisher
    ..In addition, a cell line that stably expressing URAT1 could be a useful tool for the development of uricosuric drugs. ..
  7. Roddy E, Zhang W, Doherty M. Concordance of the management of chronic gout in a UK primary-care population with the EULAR gout recommendations. Ann Rheum Dis. 2007;66:1311-5 pubmed
    ..Persistent hyperuricaemia was often seen in allopurinol non-users, but was also in allopurinol users, suggesting that doses >300 mg are often necessary. ..
  8. Price K, Sautin Y, Long D, Zhang L, Miyazaki H, Mu W, et al. Human vascular smooth muscle cells express a urate transporter. J Am Soc Nephrol. 2006;17:1791-5 pubmed
    ..It is proposed that URAT1 may provide a mechanism by which uric acid enters the human vascular smooth muscle cell, a finding that may be relevant to the role of uric acid in cardiovascular disease. ..
  9. Perez Ruiz F. Treating to target: a strategy to cure gout. Rheumatology (Oxford). 2009;48 Suppl 2:ii9-ii14 pubmed publisher
    ..In the long term, reduction in the sUA below the target level will result in gout being effectively cured. ..

More Information


  1. Yamada H, Kotaki H, Furitsu H, Sawada Y, Iga T. Mechanism of the uricosuric action of E3040, a drug used to treat inflammatory bowel disease II: study using DBA/2N mice. Biopharm Drug Dispos. 1999;20:271-6 pubmed
    ..after administration of E3040 and its conjugates, sulphate and glucuronide, with that of other general uricosuric agents in DBA/2N mice...
  2. Shoji A, Yamanaka H, Kamatani N. A retrospective study of the relationship between serum urate level and recurrent attacks of gouty arthritis: evidence for reduction of recurrent gouty arthritis with antihyperuricemic therapy. Arthritis Rheum. 2004;51:321-5 pubmed
    ..To evaluate the proposed relationship between persistent reduction of serum urate into the subsaturating range and reduction in the frequency of acute gouty attacks...
  3. Pascual E, Sivera F. Therapeutic advances in gout. Curr Opin Rheumatol. 2007;19:122-7 pubmed
    ..Promoting a proper lifestyle appears to be especially important. ..
  4. Romeijnders A, Gorter K. [Summary of the Dutch College of General Practitioners' "Gout" Standard]. Ned Tijdschr Geneeskd. 2002;146:309-13 pubmed
    ..Consultation with or referral to a rheumatologist is indicated in the case of doubt about the diagnosis of 'acute gout' or 'complicated gout', or (suspected) bacterial arthritis and insufficient treatment effect. ..
  5. Doherty M, Jansen T, Nuki G, Pascual E, Perez Ruiz F, Punzi L, et al. Gout: why is this curable disease so seldom cured?. Ann Rheum Dis. 2012;71:1765-70 pubmed publisher
  6. Mazzali M, Kanellis J, Han L, Feng L, Xia Y, Chen Q, et al. Hyperuricemia induces a primary renal arteriolopathy in rats by a blood pressure-independent mechanism. Am J Physiol Renal Physiol. 2002;282:F991-7 pubmed
    ..Thus hyperuricemia induces a renal arteriolopathy in rats that is blood pressure independent and involves the renin-angiotensin system. ..
  7. Lee M, Graham G, Williams K, Day R. 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. 2008;31:643-65 pubmed
    ..We conclude that the withdrawal of benzbromarone was not in the best interest of patients with gout. ..
  8. Bieber J, Terkeltaub R. Gout: on the brink of novel therapeutic options for an ancient disease. Arthritis Rheum. 2004;50:2400-14 pubmed
  9. El Sheikh A, van den Heuvel J, Koenderink J, Russel F. Effect of hypouricaemic and hyperuricaemic drugs on the renal urate efflux transporter, multidrug resistance protein 4. Br J Pharmacol. 2008;155:1066-75 pubmed publisher
    ..In conclusion, MRP4 may provide a potential target for drugs affecting urate homoeostasis, which needs to be further evaluated in vivo. ..
  10. Uchida S, Shimada K, Misaka S, Imai H, Katoh Y, Inui N, et al. Benzbromarone pharmacokinetics and pharmacodynamics in different cytochrome P450 2C9 genotypes. Drug Metab Pharmacokinet. 2010;25:605-10 pubmed
    ..Further studies are required to assess the clinical impact of CYP2C9 on the metabolism of benzbromarone. ..
  11. Wong M. Optimal management of chronic gout: attempting to render the (t)issues crystal-clear. N Z Med J. 2005;118:U1533 pubmed
  12. Gröbner W, Walter Sack I. [Treatment of hyperuricemia and gout]. Med Monatsschr Pharm. 2005;28:159-64; quiz 165-6 pubmed
  13. Yelken B, Caliskan Y, Gorgulu N, Altun I, Yilmaz A, Yazici H, et al. Reduction of uric acid levels with allopurinol treatment improves endothelial function in patients with chronic kidney disease. Clin Nephrol. 2012;77:275-82 pubmed
    ..96 ± 8%, p < 0.001). Treatment of hyperuricemia with allopurinol improve ED in patients with CKD. However, mechanism responsible for this beneficial effect seems to be apart from antioxidant effects of allopurinol. ..
  14. Gibbs J, Adeyeye M, Yang Z, Shen D. Valproic acid uptake by bovine brain microvessel endothelial cells: role of active efflux transport. Epilepsy Res. 2004;58:53-66 pubmed
    ..The findings also adds to the growing evidence that up-regulation of active drug efflux transporters at the BBB may contribute to the development of drug resistance to antiepileptic drug therapy. ..
  15. Daskalopoulou S, Mikhailidis D, Athyros V, Papageorgiou A, Elisaf M. Fenofibrate and losartan. Ann Rheum Dis. 2004;63:469-70 pubmed
  16. Hu J, Liu X, Xie L, Wang G, Liu H. Possible multiple transporters were involved in hepatobiliary excretion of antofloxacin in rats. Xenobiotica. 2007;37:579-91 pubmed
    ..Significant decrease in the steady state biliary clearance of ATFX and its glucuronide was observed in CCl(4)-EHI(24h) rats. 5. These results indicate that multiple transporters are possibly involved in the biliary excretion of ATFX. ..
  17. Rao G, Ramesh S, Ahmad A, Tripathi H, Sharma L, Malik J. Pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in goats given enrofloxacin alone and in combination with probenecid. Vet J. 2002;163:85-93 pubmed
    ..1 microg x mL(-1) and was maintained in plasma up to 8 h in goats after i.m. administration of enrofloxacin alone. These data indicate that a 12 h dosing regime may be appropriate for use in goats. ..
  18. Zychowicz M, Pope R, Graser E. The current state of care in gout: Addressing the need for better understanding of an ancient disease. J Am Acad Nurse Pract. 2010;22 Suppl 1:623-36 pubmed publisher
    ..Patient education can be a key element in this process. ..
  19. Fox R. [Management of recurrent gout]. Praxis (Bern 1994). 2008;97:628-9 pubmed
  20. Finley J. Case 8: initiation of urate-lowering therapy for standard advanced gout. Am J Med. 2006;119:S25-8 pubmed
  21. Csiky B, Markó L, Mohás M, Cseh J, Mikolas E, Szijártó I, et al. [The pleiotropic effects of losartan--the importance of decreasing uric acid level]. Lege Artis Med. 2008;18:663-6 pubmed
    ..The pleiotropic effects together with the blockade of the angiotensin II. receptors are considered more and more important in the hypertensive end-organ protection and in the treatment of associated diseases in hypertensive patients. ..
  22. Bibert S, Hess S, Firsov D, Thorens B, Geering K, Horisberger J, et al. Mouse GLUT9: evidences for a urate uniporter. Am J Physiol Renal Physiol. 2009;297:F612-9 pubmed publisher
    ..The well-known uricosuric agents benzbromarone (500 microM) and losartan (1 mM) inhibit GLUT9-mediated urate uptake by 90 and 50%, ..
  23. Choy G. An update on the treatment options for gout and calcium pyrophosphate deposition. Expert Opin Pharmacother. 2005;6:2443-53 pubmed
    ..Optimal treatment for both requires prompt resolution of acute synovitis, reduction of chronic joint damage and management of associated conditions. Available therapeutic interventions and future strategies are reviewed in this article. ..
  24. Castillo B, Porzgen P, Penner R, Horgen F, Fleig A. Development and optimization of a high-throughput bioassay for TRPM7 ion channel inhibitors. J Biomol Screen. 2010;15:498-507 pubmed publisher
    ..The quality of the bioassay window is excellent based on an established statistical parameter used to evaluate high-throughput screening window quality (Z and Z' factors > or =0.5). ..
  25. Grobner W, Zollner N. [Gout]. Z Rheumatol. 2004;63:2-9 pubmed
    ..consists of dietary measurements and administration of uric acid lowering drugs, such as allopurinol or uricosuric agents. Nonsteroidal antiinflammatory drugs, colchicine and glucocorticosteroids are the treatment of choice for ..
  26. Khamdang S, Takeda M, Babu E, Noshiro R, Onozato M, Tojo A, et al. Interaction of human and rat organic anion transporter 2 with various cephalosporin antibiotics. Eur J Pharmacol. 2003;465:1-7 pubmed
    ..The interaction of human-OAT2 with cephalosporins was the weakest among the basolateral human-OATs tested. In addition, it is suggested that human-OATs mediate cephaloridine-induced nephrotoxicity. ..
  27. Kamienski M. Gout: not just for the rich and famous! Everyman's disease. Orthop Nurs. 2003;22:16-20; quiz 21-2 pubmed
    ..The treatment plan and follow-up for the patient in the case presentation conclude the discussion. ..
  28. Frezzatti R, Silveira P. Allopurinol reduces the lethality associated with acute renal failure induced by Crotalus durissus terrificus snake venom: comparison with probenecid. PLoS Negl Trop Dis. 2011;5:e1312 pubmed publisher
  29. Khan M, Khan R, Islam F, Laghari J, Jamali S. To study the efficacy of Losartan on urinary uric acid excretion in Thiazide induced hyperuricemic and hypertensive patients. Pak J Pharm Sci. 2011;24:583-7 pubmed
    ..Ultimately Losartan decrease serum uric acid level and uricosuric effect of Losartan might be particularly useful in Hyperuricemic patients those on Thiazide diuretic (for hypertension and heart failure). ..
  30. Taniguchi T, Ashizawa N, Matsumoto K, Iwanaga T, Saitoh K. Uricosuric agents decrease the plasma urate level in rats by concomitant treatment with topiroxostat, a novel xanthine oxidoreductase inhibitor. J Pharm Pharmacol. 2016;68:76-83 pubmed publisher
    The aim of this study was to establish the rat model for evaluating hypouricemic effects by some uricosuric agents. Rats were made hyperuricemic by subcutaneous administration of potassium oxonate, a uricase inhibitor, or made ..
  31. Keenan R, O Brien W, Lee K, Crittenden D, Fisher M, Goldfarb D, et al. Prevalence of contraindications and prescription of pharmacologic therapies for gout. Am J Med. 2011;124:155-63 pubmed publisher
    ..Frequently, despite contraindications to gout therapies, patients are frequently prescribed these medications. ..
  32. Alvarez Fischer D, Noelker C, Grünewald A, Vulinović F, Guerreiro S, Fuchs J, et al. Probenecid potentiates MPTP/MPP+ toxicity by interference with cellular energy metabolism. J Neurochem. 2013;127:782-92 pubmed publisher
    ..Probenecid can potentiate the effect of mitochondrial toxins due to its impact on ATP metabolism and could therefore be useful to model atypical parkinsonian syndromes. ..
  33. Servais A, Lechat P, Zahr N, Urien S, Aymard G, Jaudon M, et al. [Tubular transporters OAT1 and MRP2 and clearance of adefovir]. Nephrol Ther. 2005;1:296-300 pubmed
    ..Additional pharmacological inhibition of transporters decreased renal clearance, which may reflect inhibition of compensating transport mechanisms activated when MRP2 is lacking. ..
  34. Terkeltaub R, Bushinsky D, Becker M. Recent developments in our understanding of the renal basis of hyperuricemia and the development of novel antihyperuricemic therapeutics. Arthritis Res Ther. 2006;8 Suppl 1:S4 pubmed
    ..For this reason, our discussion focuses on the development of the novel xanthine oxidase inhibitor febuxostat and modified recombinant uricase preparations. ..
  35. Hosoyamada M, Shibasaki T, Ichida K. [Molecular mechanism in biological transport in the kidney: Urate transporter URAT1]. Nihon Rinsho. 2006;64 Suppl 2:176-9 pubmed
  36. Yan H, Ma Y, Liu M, Zhou L. The dual actions of Paederia scandens extract as a hypouricemic agent: xanthine oxidase inhibitory activity and uricosuric effect. Planta Med. 2008;74:1345-50 pubmed publisher
    ..The potential application of this compound in the treatment of conditions associated with hyperuricemia is discussed. ..
  37. Caforio A, Gambino A, Tona F, Feltrin G, Marchini F, Pompei E, et al. Sulfinpyrazone reduces cyclosporine levels: a new drug interaction in heart transplant recipients. J Heart Lung Transplant. 2000;19:1205-8 pubmed
    ..In HT recipients sulfinpyrazone, as an alternative to allopurinol, is effective in achieving metabolic control of hyperuricemia. However, this drug reduced CsA levels, thus the risk of rejection is present. ..
  38. Takeda M, Narikawa S, Hosoyamada M, Cha S, Sekine T, Endou H. Characterization of organic anion transport inhibitors using cells stably expressing human organic anion transporters. Eur J Pharmacol. 2001;419:113-20 pubmed
    ..In contrast, KW-3902 did not exert the effects of significance, whereas KW-3902 was the most potent. ..
  39. Fast V, Ideker R. Simultaneous optical mapping of transmembrane potential and intracellular calcium in myocyte cultures. J Cardiovasc Electrophysiol. 2000;11:547-56 pubmed
    ..The results demonstrate feasibility of simultaneous optical recordings of Vm and Ca(i)2+ transients with high spatial and temporal resolution. ..
  40. Harris M, Bryant L, Danaher P, Alloway J. Effect of low dose daily aspirin on serum urate levels and urinary excretion in patients receiving probenecid for gouty arthritis. J Rheumatol. 2000;27:2873-6 pubmed
    ..05, paired t test). Low dose daily enteric coated aspirin does not significantly interfere with the uricosuric effects of probenecid in patients with gouty arthritis. ..
  41. Suresh E, Das P. Recent advances in management of gout. QJM. 2012;105:407-17 pubmed publisher
    ..Several other drugs with rational mechanisms of action are in the pipeline, and likely to be introduced over the next few years. A new era has thus begun in the field of gout. ..
  42. Adachi N, Lei B, Deshpande G, Seyfried F, Shimizu I, Nagaro T, et al. Uraemia suppresses central dopaminergic metabolism and impairs motor activity in rats. Intensive Care Med. 2001;27:1655-60 pubmed
    ..The turnover of NE and 5-hydroxytryptamine (5-HT) was unchanged in all regions examined. Suppression of the central DA turnover appears to be involved in the impairment of motor activity in uraemic rats. ..
  43. Dubost J, Mathieu S, Soubrier M. [Treatment of gout]. Rev Med Interne. 2011;32:751-7 pubmed publisher
    ..Education of patient, identification and correction of cardiovascular risk factors should not be forgotten. ..
  44. Okuda C, Koyama H, Tsutsumi Z, Yamamoto A, Kurajoh M, Moriwaki Y, et al. Serum CRP in patients with gout and effects of benzbromarone. Int J Clin Pharmacol Ther. 2011;49:191-7 pubmed
    ..These results suggest that hyperuricemia may not contribute to an increase in serum CRP level, while benzbromarone may have a favorable effect on CRP. ..
  45. Potschka H, Fedrowitz M, Loscher W. P-glycoprotein and multidrug resistance-associated protein are involved in the regulation of extracellular levels of the major antiepileptic drug carbamazepine in the brain. Neuroreport. 2001;12:3557-60 pubmed
    ..The data indicate that both PGP and MRP participate in the regulation of extracellular brain concentrations of the major AED carbamazepine. ..
  46. Beyer J, Bierl A, Peters F, Maurer H. Screening procedure for detection of diuretics and uricosurics and/or their metabolites in human urine using gas chromatography-mass spectrometry after extractive methylation. Ther Drug Monit. 2005;27:509-20 pubmed
    ..The procedure described here is part of a systematic toxicological analysis procedure for acidic drugs and poisons. ..
  47. Petroske E, Meredith G, Callen S, Totterdell S, Lau Y. Mouse model of Parkinsonism: a comparison between subacute MPTP and chronic MPTP/probenecid treatment. Neuroscience. 2001;106:589-601 pubmed
    ..It should also prove useful for the development of neuroprotection strategies. ..
  48. Shin Y, Lee J, Oh J, Lee Y. Low-dose probenecid selectively inhibits urinary excretion of phenolsulfonphthalein in rats without affecting biliary excretion. J Appl Toxicol. 2013;33:511-5 pubmed publisher
    ..These data suggest that a low dose of probenecid selectively inhibits urinary excretion of PSP that may be mediated by organic anion transporters, without affecting biliary excretion that may be mediated by Mrp2. ..
  49. Stocker S, Graham G, McLachlan A, Williams K, Day R. Pharmacokinetic and pharmacodynamic interaction between allopurinol and probenecid in patients with gout. J Rheumatol. 2011;38:904-10 pubmed publisher
    ..Australian Clinical Trials Registry ACTRN012606000276550. ..
  50. Ogino K, Hisatome I, Shigemasa C. [Anti hyperuricemic agents]. Nihon Rinsho. 2003;61 Suppl 1:197-201 pubmed
  51. Murakami H, Shimamoto K. [Essential hypertension]. Nihon Rinsho. 2003;61 Suppl 1:235-40 pubmed
  52. Zalups R, Ahmad S. Handling of cysteine S-conjugates of methylmercury in MDCK cells expressing human OAT1. Kidney Int. 2005;68:1684-99 pubmed
  53. Zhu Y, Meng Q, Wang C, Liu Q, Sun H, Kaku T, et al. Organic anion transporters involved in the excretion of bestatin in the kidney. Peptides. 2012;33:265-71 pubmed publisher
    ..Our results are novel in demonstrating for the first time that OAT1 and OAT3 are involved in the renal excretion of bestatin. ..