Pharmacokinetics and pharmacodynamics of intravenous PEGylated recombinant mammalian urate oxidase in patients with refractory gout

Arthritis Rheum. 2007 Mar;56(3):1021-8. doi: 10.1002/art.22403.


Objective: To evaluate the efficacy, immunogenicity, and tolerability of intravenous (IV) PEGylated recombinant mammalian urate oxidase (PEG-uricase) for the treatment of severe gout.

Methods: Single infusions of PEG-uricase (at doses ranging from 0.5 mg to 12 mg) were administered to 24 patients (6 cohorts of 4 patients each) in a phase I clinical trial. Plasma uricase activity (pUox), the plasma urate concentration (pUAc), and the uric acid-to-creatinine ratio (UAc:Cr) in urine were monitored for 21 days after dosing. Adverse events and the IgG antibody response to PEG-uricase were followed up for 35 days.

Results: All patients completed the trial. Maximum pUox was linearly related to the IV dose of PEG-uricase, the area under the curve (AUC) value increased linearly (up to a dose of 8 mg), and the pUox half-life was 6.4-13.8 days. After doses of 4-12 mg, the pUAc fell within 24-72 hours, from a mean +/- SD value of 11.1 +/- 0.6 mg/dl to 1.0 +/- 0.5 mg/dl; the AUC value for the pUAc was equivalent to maintaining the pUAc at 1.2-4.7 mg/dl for 21 days postinfusion. The UAc:Cr ratio in urine fell in parallel with the pUAc. IgG antibodies to PEG-uricase, mostly IgG2 and specific for PEG, developed in 9 patients, who had more rapid enzyme clearance but no allergic reactions. All adverse events were mild to moderate, with gout flares being most common.

Conclusion: The bioavailability, efficacy, and tolerability of IV PEG-uricase were greater than the bioavailability, efficacy, and tolerability observed in a previous phase I trial of subcutaneous PEG-uricase. Infusing 4-12 mg of PEG-uricase every 2-4 weeks should maintain the pUAc well below the therapeutic target of 6 mg/dl and greatly reduce renal uric acid excretion. This treatment could be effective in depleting expanded tissue urate stores in patients with chronic or tophaceous gout.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies / immunology
  • Antibodies / metabolism
  • Creatinine / urine
  • Dose-Response Relationship, Drug
  • Female
  • Gout / drug therapy*
  • Gout Suppressants / administration & dosage*
  • Gout Suppressants / adverse effects
  • Gout Suppressants / immunology
  • Gout Suppressants / pharmacokinetics*
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Polyethylene Glycols / administration & dosage*
  • Polyethylene Glycols / adverse effects
  • Polyethylene Glycols / pharmacokinetics*
  • Urate Oxidase / administration & dosage*
  • Urate Oxidase / adverse effects
  • Urate Oxidase / immunology
  • Urate Oxidase / pharmacokinetics*
  • Uric Acid / urine


  • Antibodies
  • Gout Suppressants
  • Uric Acid
  • Polyethylene Glycols
  • Creatinine
  • Urate Oxidase
  • Pegloticase