title: Pharmacokinetics and pharmacodynamics of pegloticase in patients with end-stage renal failure receiving hemodialysis.
abstract: OBJECTIVE
  Phase 3 trial data indicate that treatment of chronic tophaceous gout with pegloticase, a recombinant uricase conjugated to polyethylene glycol, does not reduce estimated glomerular filtration rate in chronic kidney disease (CKD) patients and that pegloticase therapeutics are independent of CKD stages 1 - 4. We determined the pharmacokinetics/pharmacodynamics of pegloticase after a single-dose in non-gout subjects with stage 5 CKD receiving hemodialysis.
  
  
  METHODS
  In this open-label phase 1 study, 12 subjects received a single intravenous dose of pegloticase 8 mg 3 hours prior to hemodialysis. Blood samples for determination of serum pegloticase concentrations and serum uric acid (SUA) levels were collected immediately predose and at regular intervals before, during, and after hemodialysis.
  
  
  RESULTS
  Mean serum pegloticase concentrations remained stable and were unaffected by dialysis sessions. Mean SUA fell to undetectable levels within 3 hours and remained undetected for up to 72 hours postdose.
  
  
  CONCLUSIONS
  Our findings indicate no significant effect of hemodialysis on either the stability of serum pegloticase concentrations after a single dose or the capacity of pegloticase to lower SUA. No new safety signals were detected. Administration of pegloticase in patients with comorbid chronic tophaceous gout and endstage renal failure requiring hemodialysis appears feasible.
authors: Anthony J
authors: AJ
authors: Bleyer
authors: David
authors: D
authors: Wright
authors: Harry
authors: H
authors: Alcorn
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D016903:Drug Monitoring; D005260:Female; D006074:Gout Suppressants / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D007262:Infusions, Intravenous; D007676:Kidney Failure, Chronic / Q000097:blood / Q000175:diagnosis / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D006435:Renal Dialysis / Q000009:adverse effects; D018570:Risk Assessment; D014503:Urate Oxidase / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D014527:Uric Acid / Q000097:blood
chemical_list: D015415:Biomarkers; D006074:Gout Suppressants; D014527:Uric Acid; D011092:Polyethylene Glycols; D014503:Urate Oxidase; C031545:Pegloticase