Skip to main content
SpringerLink
Log in

Clinical Pharmacokinetics and Pharmacodynamics of Febuxostat

  • Review Article
  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

Abstract

Febuxostat is a xanthine oxidoreductase inhibitor that has been developed to treat chronic gout. In healthy subjects, the pharmacokinetic parameters of febuxostat after multiple oral dose administration include an oral availability of about 85 %, an apparent oral clearance (CL/F) of 10.5 ± 3.4 L/h and an apparent volume of distribution at steady state (V ss/F) of 48 ± 23 L. The time course of plasma concentrations follows a two-compartment model. The initial half-life (t ½) is approximately 2 h and the terminal t ½ determined at daily doses of 40 mg or more is 9.4 ± 4.9 h. Febuxostat is administered once daily. The maximum (peak) plasma concentrations are approximately 100-fold greater than the trough concentrations. Consequently, there is no significant accumulation of the drug during multiple dose administration. There are few data on the pharmacokinetics of febuxostat in patients with gout. While the pharmacokinetic parameters are not affected by mild to moderate hepatic impairment, there is no consensus on whether renal impairment has any effect on the pharmacokinetics of febuxostat. Febuxostat is extensively metabolised by oxidation (approximately 35 %) and acyl glucuronidation (up to 40 %); febuxostat acyl glucuronides are cleared by the kidney. In healthy subjects treated with multiple doses of febuxostat 10–240 mg, the concentrations of serum urate are reduced by a maximum of about 80 %. The percentage reduction in the concentrations of serum urate is slightly less in gouty patients than in healthy subjects.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Loeb JN. The influence of temperature on the solubility of monosodium urate. Arthritis Rheum. 1972;15(2):189–92.

    Article  CAS  PubMed  Google Scholar 

  2. Khosravan R, Grabowski BA, Wu JT, Joseph-Ridge N, Vernillet L. Pharmacokinetics, pharmacodynamics and safety of febuxostat, a non-purine selective inhibitor of xanthine oxidase, in a dose escalation study in healthy subjects. Clin Pharmacokinet. 2006;45(8):821–41.

    Article  CAS  PubMed  Google Scholar 

  3. Grabowski B, Khosravan R, Wu JT, Vernillet L, Lademacher C. Effect of hydrochlorothiazide on the pharmacokinetics and pharmacodynamics of febuxostat, a non-purine selective inhibitor of xanthine oxidase. Br J Clin Pharmacol. 2010;70(1):57–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Grabowski BA, Khosravan R, Vernillet L, Mulford DJ. Metabolism and excretion of [14C] febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase, in healthy male subjects. J Clin Pharmacol. 2011;51(2):189–201.

    Article  CAS  PubMed  Google Scholar 

  5. Khosravan R, Grabowski B, Wu JT, Joseph-Ridge N, Vernillet L. Effect of food or antacid on pharmacokinetics and pharmacodynamics of febuxostat in healthy subjects. Br J Clin Pharmacol. 2008;65(3):355–63.

    Article  CAS  PubMed  Google Scholar 

  6. Khosravan R, Grabowski BA, Mayer MD, Wu JT, Joseph-Ridge N, Vernillet L. The effect of mild and moderate hepatic impairment on pharmacokinetics, pharmacodynamics, and safety of febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase. J Clin Pharmacol. 2006;46(1):88–102.

    Article  CAS  PubMed  Google Scholar 

  7. Mayer MD, Khosravan R, Vernillet L, Wu JT, Joseph-Ridge N, Mulford DJ. Pharmacokinetics and pharmacodynamics of febuxostat, a new non-purine selective inhibitor of xanthine oxidase in subjects with renal impairment. Am J Ther. 2005;12(1):22–34.

    Article  PubMed  Google Scholar 

  8. Liu XX, Liu RJ, Ding L, Lin YF, Huang NY, Xiao HF, et al. Pharmacokinetics of febuxostat in healthy Chinese volunteers. Arzneimittelforschung. 2012;62(10):463–9.

    Article  CAS  PubMed  Google Scholar 

  9. Hosoya T, Ohno I. A repeated oral administration study of febuxostat (TMX-67), a non-purine-selective inhibitor of xanthine oxidase, in patients with impaired renal function in Japan: pharmacokinetic and pharmacodynamic study. J Clin Rheumatol. 2011;17(4 Suppl 2):S27–34.

    PubMed  Google Scholar 

  10. Khosravan R, Kukulka MJ, Wu JT, Joseph-Ridge N, Vernillet L. The effect of age and gender on pharmacokinetics, pharmacodynamics, and safety of febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase. J Clin Pharmacol. 2008;48(9):1014–24.

    Article  CAS  PubMed  Google Scholar 

  11. Zhou H, Zheng Y, Wu G, Hu X, Zhai Y, Iv D, et al. Pharmacokinetics and tolerability of febuxostat after oral administration in healthy Chinese volunteers: a randomized, open-label, singleand multiple-dose three-way crossover study. Int J Clin Pharmacol Ther. 2016;54(2):115–24.

    Article  CAS  PubMed  Google Scholar 

  12. Sheiner LB, Benet LZ, Pagliaro LA. A standard approach to compiling clinical pharmacokinetic data. J Pharmacokinet Biopharm. 1981;9(1):59–127.

    Article  CAS  PubMed  Google Scholar 

  13. Purves RD. Multiple solutions, illegal parameter values, local minima of the sum of squares, and anomalous parameter estimates in least-squares fitting of the two-compartment pharmacokinetic model with absorption. J Pharmacokinet Biopharm. 1996;24(1):79–101.

    Article  CAS  PubMed  Google Scholar 

  14. Khosravan R, Wu JT, Joseph-Ridge N, Vernillet L. Population pharmacokinetics and pharmacodynamics of febuxostat in a phase III study of patients with gout [abstract]. Clin Pharmacol Ther. 2006;79(2):21.

    Article  Google Scholar 

  15. Hira D, Chisaki Y, Noda S, Araki H, Uzu T, Maegawa H, et al. Population pharmacokinetics and therapeutic efficacy of febuxostat in patients with severe renal impairment. Pharmacology. 2015;96(1–2):90–8.

    Article  CAS  PubMed  Google Scholar 

  16. Mukoyoshi M, Nishimura S, Hoshide S, Umeda S, Kanou M, Taniguchi K, et al. In vitro drug-drug interaction studies with febuxostat, a novel non-purine selective inhibitor of xanthine oxidase: plasma protein binding, identification of metabolic enzymes and cytochrome P450 inhibition. Xenobiotica. 2008;38(5):496–510.

    Article  CAS  PubMed  Google Scholar 

  17. Gibaldi M, Boyes RN, Feldman S. Influence of first-pass effect on availability of drugs on oral administration. J Pharm Sci. 1971;60(9):1338–40.

    Article  CAS  PubMed  Google Scholar 

  18. Sallustio BC, Purdie YJ, Birkett DJ, Meffin PJ. Effect of renal dysfunction on the individual components of the acyl-glucuronide futile cycle. J Pharmacol Exp Ther. 1989;251(1):288–94.

    CAS  PubMed  Google Scholar 

  19. Meffin PJ, Zilm DM, Veenendaal JR. A renal mechanism for the clofibric acid-probenecid interaction. J Pharmacol Exp Ther. 1983;227(3):739–42.

    CAS  PubMed  Google Scholar 

  20. Veenendaal JR, Brooks PM, Meffin PJ. Probenecid-clofibrate interaction. Clin Pharmacol Ther. 1981;29(3):351–8.

    Article  CAS  PubMed  Google Scholar 

  21. Bailey MJ, Dickinson RG. Acyl glucuronide reactivity in perspective: biological consequences. Chem Biol Interact. 2003;145(2):117–37.

    Article  CAS  PubMed  Google Scholar 

  22. Hoshide S, Takahashi Y, Ishikawa T, Kubo J, Tsuchimoto M, Komoriya K, et al. PK/PD and safety of a single dose of TMX-67 (febuxostat) in subjects with mild and moderate renal impairment. Nucleosides Nucleotides Nucleic Acids. 2004;23(8–9):1117–8.

    Article  CAS  PubMed  Google Scholar 

  23. Komoriya K, Hoshide S, Takeda K, Kobayashi H, Kubo J, Tsuchimoto M, et al. Pharmacokinetics and pharmacodynamics of febuxostat (TMX-67), a non-purine selective inhibitor of xanthine oxidase/xanthine dehydrogenase (NPSIXO) in patients with gout and/or hyperuricemia. Nucleosides Nucleotides Nucleic Acids. 2004;23(8–9):1119–22.

    Article  CAS  PubMed  Google Scholar 

  24. Okamoto K, Eger BT, Nishino T, Kondo S, Pai EF, Nishino T. An extremely potent inhibitor of xanthine oxidoreductase. Crystal structure of the enzyme-inhibitor complex and mechanism of inhibition. J Biol Chem. 2003;278(3):1848–55.

    Article  CAS  PubMed  Google Scholar 

  25. Okamoto K, Eger BT, Nishino T, Pai EF, Nishino T. Mechanism of inhibition of xanthine oxidoreductase by allopurinol: crystal structure of reduced bovine milk xanthine oxidoreductase bound with oxipurinol. Nucleosides Nucleotides Nucleic Acids. 2008;27(6):888–93.

    Article  CAS  PubMed  Google Scholar 

  26. Osada Y, Tsuchimoto M, Fukushima H, Takahashi K, Kondo S, Hasegawa M, et al. Hypouricemic effect of the novel xanthine oxidase inhibitor, TEI-6720, in rodents. Eur J Pharmacol. 1993;241(2–3):183–8.

    Article  CAS  PubMed  Google Scholar 

  27. Takano Y, Hase-Aoki K, Horiuchi H, Zhao L, Kasahara Y, Kondo S, et al. Selectivity of febuxostat, a novel non-purine inhibitor of xanthine oxidase/xanthine dehydrogenase. Life Sci. 2005;76(16):1835–47.

    Article  CAS  PubMed  Google Scholar 

  28. Becker MA, Kisicki J, Khosravan R, Wu J, Mulford D, Hunt B, et al. Febuxostat (TMX-67), a novel, non-purine, selective inhibitor of xanthine oxidase, is safe and decreases serum urate in healthy volunteers. Nucleosides Nucleotides Nucleic Acids. 2004;23(8–9):1111–6.

    Article  CAS  PubMed  Google Scholar 

  29. Becker MA, Schumacher HR, Espinoza LR, Wells AF, MacDonald P, Lloyd E, et al. The urate-lowering efficacy and safety of febuxostat in the treatment of the hyperuricemia of gout: the CONFIRMS trial. Arthritis Res Ther. 2010;12(2):R63.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Becker MA, Schumacher HR, MacDonald PA, Lloyd E, Lademacher C. Clinical efficacy and safety of successful longterm urate lowering with febuxostat or allopurinol in subjects with gout. J Rheumatol. 2009;36(6):1273–82.

    Article  CAS  PubMed  Google Scholar 

  31. Becker MA, Schumacher HR Jr, Wortmann RL, MacDonald PA, Eustace D, Palo WA, et al. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. N Engl J Med. 2005;353(23):2450–61.

    Article  CAS  PubMed  Google Scholar 

  32. Becker MA, Schumacher HR Jr, Wortmann RL, MacDonald PA, Palo WA, Eustace D, et al. Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase: a twenty-eight-day, multicenter, phase II, randomized, double-blind, placebo-controlled, dose-response clinical trial examining safety and efficacy in patients with gout. Arthritis Rheum. 2005;52(3):916–23.

    Article  CAS  PubMed  Google Scholar 

  33. Schumacher HR Jr, Becker MA, Lloyd E, MacDonald PA, Lademacher C. Febuxostat in the treatment of gout: 5-yr findings of the FOCUS efficacy and safety study. Rheumatology (Oxford). 2009;48(2):188–94.

    Article  CAS  PubMed  Google Scholar 

  34. Schumacher HR Jr, Becker MA, Wortmann RL, Macdonald PA, Hunt B, Streit J, et al. Effects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: a 28-week, phase III, randomized, double-blind, parallel-group trial. Arthritis Rheum. 2008;59(11):1540–8.

    Article  CAS  PubMed  Google Scholar 

  35. Clinical pharmacology and biopharmaceutics reviews of febuxostat. Department of Health and Human Services; Food and Drug Administration (FDA); 2008. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/021856s000_ClinPharmR_P1.pdf. Accessed 10 Mar 2016.

  36. Schumacher HR Jr. Febuxostat: a non-purine, selective inhibitor of xanthine oxidase for the management of hyperuricaemia in patients with gout. Expert Opin Investig Drugs. 2005;14(7):893–903.

    Article  CAS  PubMed  Google Scholar 

  37. Sun Y, Li L, Tian-yan Z, Lu W. A model-based meta-analysis to compare urate-lowering response rate of febuxostat and allopurinol in gout patients [abstract]. Acta Pharmaceutica Sinica. 2014;49(12):1674–83.

    CAS  PubMed  Google Scholar 

  38. Sun Y, Li L, Marshall S, Lu W, Xie R. Relationship between the dose of urate lowering therapies and serum uric acid in healthy volunteers and gout patients: a model based meta-analysis (MBMA) [abstract]. Population Approach Group in Europe (PAGE). June 2015. http://www.page-meeting.org/?abstract=3513#. Accessed 7 Apr 2016.

  39. Zhang W, Doherty M, Bardin T, Pascual E, Barskova V, Conaghan P, et al. EULAR evidence based recommendations for gout. Part II: management. Report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis. 2006;65(10):1312–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Jordan KM, Cameron JS, Snaith M, Zhang W, Doherty M, Seckl J, et al. British Society for Rheumatology and British Health Professionals in Rheumatology guideline for the management of gout. Rheumatology (Oxford). 2007;46(8):1372–4.

    Article  PubMed  Google Scholar 

  41. Zhang M, Di X, Xu L, Xu J, Yang Y, Jiang N, et al. Pharmacokinetics and pharmacodynamics of febuxostat under fasting conditions in healthy individuals. Exp Ther Med. 2014;7:393–6.

    CAS  PubMed  Google Scholar 

  42. Day RO, Graham GG, Hicks M, McLachlan AJ, Stocker SL, Williams KM. Clinical pharmacokinetics and pharmacodynamics of allopurinol and oxypurinol. Clin Pharmacokinet. 2007;46(8):623–44.

    Article  CAS  PubMed  Google Scholar 

  43. Zyloprim (allopurinol) product information. The Therapeutic Goods Adminstration (TGA). 22 Feb 2016. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/PICMI?OpenForm&t=&q=allopurinol. Accessed 10 Mar 2016.

  44. Graham GG, Kannangara DR, Stocker SL, Portek I, Pile KD, Indraratna PL, et al. Understanding the dose-response relationship of allopurinol: predicting the optimal dosage. Br J Clin Pharmacol. 2013;76(6):932–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Jennings CG, Mackenzie IS, Flynn R, Ford I, Nuki G, De Caterina R, et al. Up-titration of allopurinol in patients with gout. Semin Arthritis Rheum. 2014;44(1):25–30.

    Article  CAS  PubMed  Google Scholar 

  46. Stamp LK, O’Donnell JL, Zhang M, James J, Frampton C, Barclay ML, et al. Using allopurinol above the dose based on creatinine clearance is effective and safe in patients with chronic gout, including those with renal impairment. Arthritis Rheum. 2011;63(2):412–21.

    Article  CAS  PubMed  Google Scholar 

  47. Jackson RL, Hunt B, MacDonald PA. The efficacy and safety of febuxostat for urate lowering in gout patients ≥65 years of age. BMC Geriatr. 2012;12:11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Tausche AK, Reuss-Borst M, Koch U. Urate lowering therapy with febuxostat in daily practice-a multicentre, open-label, prospective observational study. Int J Rheumatol. 2014;2014:123105.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Huang X, Du H, Gu J, Zhao D, Jiang L, Li X, et al. An allopurinol-controlled, multicenter, randomized, double-blind, parallel between-group, comparative study of febuxostat in Chinese patients with gout and hyperuricemia. Int J Rheum Dis. 2014;17(6):679–86.

    Article  CAS  PubMed  Google Scholar 

  50. Kamatani N, Fujimori S, Hada T, Hosoya T, Kohri K, Nakamura T, et al. An allopurinol-controlled, randomized, double-dummy, double-blind, parallel between-group, comparative study of febuxostat (TMX-67), a non-purine-selective inhibitor of xanthine oxidase, in patients with hyperuricemia including those with gout in Japan: phase 3 clinical study. J Clin Rheumatol. 2011;17(4 Suppl 2):S13–8.

    Article  PubMed  Google Scholar 

  51. Kamatani N, Fujimori S, Hada T, Hosoya T, Kohri K, Nakamura T, et al. An allopurinol-controlled, multicenter, randomized, open-label, parallel between-group, comparative study of febuxostat (TMX-67), a non-purine-selective inhibitor of xanthine oxidase, in patients with hyperuricemia including those with gout in Japan: phase 2 exploratory clinical study. J Clin Rheumatol. 2011;17(4 Suppl 2):S44–9.

    PubMed  Google Scholar 

  52. Kamatani N, Fujimori S, Hada T, Hosoya T, Kohri K, Nakamura T, et al. Multicenter, open-label study of long-term administration of febuxostat (TMX-67) in Japanese patients with hyperuricemia including gout. J Clin Rheumatol. 2011;17(4 Suppl 2):S50–6.

    Article  PubMed  Google Scholar 

  53. Keenan RT, O’Brien WR, Lee KH, Crittenden DB, Fisher MC, Goldfarb DS, et al. Prevalence of contraindications and prescription of pharmacologic therapies for gout. Am J Med. 2011;124(2):155–63.

    Article  PubMed  Google Scholar 

  54. Fleischmann R, Kerr B, Yeh LT, Suster M, Shen Z, Polvent E, et al. Pharmacodynamic, pharmacokinetic and tolerability evaluation of concomitant administration of lesinurad and febuxostat in gout patients with hyperuricaemia. Rheumatology (Oxford). 2014;53(12):2167–74.

    Article  PubMed  Google Scholar 

  55. Perez-Ruiz F, Sundy JS, Miner JN, Cravets M, Storgard C, Group RS. Lesinurad in combination with allopurinol: results of a phase 2, randomised, double-blind study in patients with gout with an inadequate response to allopurinol. Ann Rheum Dis. 2016;75(6):1074–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Saag KG, Fitz-Patrick D, Kopicko J, Fung M, Bhakta N, Adler S, et al. Lesinurad combined with allopurinol: randomized, double-blind, placebo-controlled study in gout subjects with inadequate response to standard of care allopurinol (a US-based study). Arthritis Rheumatol. 2016. doi:10.1002/art.39840 (Epub 2016 Aug 26).

    Google Scholar 

  57. Stocker SL, Graham GG, McLachlan AJ, Williams KM, Day RO. Pharmacokinetic and pharmacodynamic interaction between allopurinol and probenecid in patients with gout. J Rheumatol. 2011;38(5):904–10.

    Article  CAS  PubMed  Google Scholar 

  58. Bianchi R, Vitali C, Clerico A, Pilo A, Riente L, Fusani L, et al. Uric acid metabolism in normal subjects and in gouty patients by chromatographic measurement of 14C-uric acid in plasma and urine. Metabolism. 1979;28(11):1105–13.

    Article  CAS  PubMed  Google Scholar 

  59. Khosravan R, Wu JT, Joseph-Ridge N, Vernillet L. Pharmacokinetic interactions of concomitant administration of febuxostat and NSAIDs. J Clin Pharmacol. 2006;46(8):855–66.

    Article  CAS  PubMed  Google Scholar 

  60. Khosravan R, Mayer MD, Wu JT, Josephridge N, Vernillet L. Effect of concomitant administration of febuxostat and colchicine on pharmacokinetics of febuxostat and colchicine at steady state. Arthritis Rheum. 2005;52(9):S102–3.

    Google Scholar 

  61. Khosravan R, Erdman K, Vernillet L, Wu JT, Josephridge N, Umeda S, et al. Effect of febuxostat on pharmacokinetics of desipramine, a CYP2D6 substrate, in healthy subjects [abstract]. Clin Pharmacol Ther. 2005;77(2):43.

    Article  Google Scholar 

  62. Summary of product characteristics: Adenuric 80 mg film coated tablets. European Medicines Agency; 2012. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000777/WC500021812.pdf. Accessed 10 Mar 2016.

  63. Perez-Ruiz F, Chinchilla SP, Atxotegi J, Urionaguena I, Herrero-Beites AM, Aniel-Quiroga MA. Increase in thyroid stimulating hormone levels in patients with gout treated with inhibitors of xanthine oxidoreductase. Rheumatol Int. 2015;35(11):1857–61.

    Article  CAS  PubMed  Google Scholar 

  64. Khanna D, Khanna PP, Fitzgerald JD, Singh MK, Bae S, Neogi T, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 2: therapy and antiinflammatory prophylaxis of acute gouty arthritis. Arthritis Care Res (Hoboken). 2012;64(10):1447–61.

  65. Signal: febuxostat and hepatic failure. World Health Organization (WHO). WHO Pharmaceuticals Newsletter. 2013;2:11–12. http://www.who.int/medicines/publications/NewsletterNo2_2013EC.pdf. Accessed 10 Mar 2016.

  66. Ito K, Ueda Y, Miyazawa H, Kaku Y, Hirai K, Hoshino T, et al. Acute severe liver dysfunction induced by febuxostat in a patient undergoing hemodialysis. CEN Case Reports. 2014;3(2):158–61.

    Article  Google Scholar 

  67. Febuxostat safety reports. Pharmacovigilance Insight. Springer 2013. Available from: http://adisinsight.springer.com. Accessed 18 June 2014.

  68. MacDonald TM, Ford I, Nuki G, Mackenzie IS, De Caterina R, Findlay E, et al. Protocol of the Febuxostat versus Allopurinol Streamlined Trial (FAST): a large prospective, randomised, open, blinded endpoint study comparing the cardiovascular safety of allopurinol and febuxostat in the management of symptomatic hyperuricaemia. BMJ Open. 2014;4(7):e005354.

    Article  PubMed  PubMed Central  Google Scholar 

  69. White WB, Chohan S, Dabholkar A, Hunt B, Jackson R. Cardiovascular safety of febuxostat and allopurinol in patients with gout and cardiovascular comorbidities. Am Heart J. 2012;164(1):14–20.

    Article  CAS  PubMed  Google Scholar 

  70. Chohan S. Safety and efficacy of febuxostat treatment in subjects with gout and severe allopurinol adverse reactions. J Rheumatol. 2011;38(9):1957–9.

    Article  CAS  PubMed  Google Scholar 

  71. Dore M, Frenette AJ, Mansour AM, Troyanov Y, Begin J. Febuxostat as a novel option to optimize thiopurines’ metabolism in patients with inadequate metabolite levels. Ann Pharmacother. 2014;48(5):648–51.

    Article  PubMed  Google Scholar 

  72. Kumari R, Timshina DK, Thappa DM. Drug hypersensitivity syndrome. Indian J Dermatol Venereol Leprol. 2011;77(1):7–15.

    Article  PubMed  Google Scholar 

  73. Safety of medicines: febuxostat and agranulocytosis. World Health Organization. WHO Pharmaceuticals Newsletter. 2015;4:16. http://www.who.int/medicines/publications/Pharm_Newsletter4_2015.pdf. Accessed 10 Mar 2016.

  74. Kobayashi S, Ogura M, Hosoya T. Acute neutropenia associated with initiation of febuxostat therapy for hyperuricaemia in patients with chronic kidney disease. J Clin Pharm Ther. 2013;38(3):258–61.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia

    Bishoy Kamel, Garry G. Graham, Kenneth M. Williams & Richard O. Day

  2. Department of Clinical Pharmacology and Toxicology, Level 2 Xavier Building, St Vincent’s Hospital, 390 Victoria Street, Darlinghurst, NSW, 2010, Australia

    Bishoy Kamel, Garry G. Graham, Kenneth M. Williams & Richard O. Day

  3. Department of Medicine, Western Sydney University, Campbelltown, NSW, Australia

    Kevin D. Pile

  4. St Vincent’s Clinical School, University of New South Wales, Sydney, NSW, Australia

    Richard O. Day

Authors
  1. Bishoy Kamel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Garry G. Graham
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kenneth M. Williams
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kevin D. Pile
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Richard O. Day
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Richard O. Day.

Ethics declarations

Funding

No sources of external funding were used to prepare this review.

Conflict of interest

Bishoy Kamel, Garry G. Graham, Kenneth M. Williams, Kevin D. Pile and Richard O. Day declare no conflict of interest that is directly relevant to the content of this review. K.D. Pile, K.M. Williams and R.O. Day are Investigators on a National Health and Medical Research Council (NH&MRC) Partnership Grant (#1094708; 2015–16) investigating whether response rates to urate-lowering therapy can be increased in primary care. Menarini Australia, makers of febuxostat, and AstraZeneca Pty Ltd, makers of lesinurad, are two of seven partners in the coordinated grant. The rules for avoidance of conflicts of interest with commercial partners are clearly stated by the NH&MRC and have not been violated.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kamel, B., Graham, G.G., Williams, K.M. et al. Clinical Pharmacokinetics and Pharmacodynamics of Febuxostat. Clin Pharmacokinet 56, 459–475 (2017). https://doi.org/10.1007/s40262-016-0466-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40262-016-0466-4

Keywords

Search

Navigation