title: Efficacy and (pharmaco)kinetics of one single dose of rasburicase in patients with chronic kidney disease.
abstract: OBJECTIVE
  Hyperuricemia is a risk factor associated with cardiovascular and renal disease. Recently, rasburicase, a recombinant urate oxidase, has been developed for the treatment of hyperuricemia in patients with primarily hematological malignancies. We studied the pharmacokinetics and metabolism of rasburicase in the treatment of chronic asymptomatic hyperuricemia in chronic kidney disease (CKD) patients.
  
  
  METHODS
  We studied 9 CKD patients with hyperuricemia, whose mean serum acid concentration was 10.2 (range 8.3-15.8) mg/dl. No study subject was taking allopurinol (3/9 are allopurinol intolerant). Patients were treated with rasburicase (0.2 mg/kg/day) in single dose by intravenous infusion over a 30-min period. Serum samples were collected after 1, 4, 8, 24, 48 and 72 h, after 1 week, and after 1 month. To evaluate the efficacy of rasburicase, plasma and urinary concentrations of uric acid were determined by the standard method; the plasma activity of rasburicase was determined using a new assay developed by our laboratory (chromatography-mass method, a colorimetric 96-well microtiter plate assay).
  
  
  RESULTS
  All the treated patients experienced a rapid reduction in their plasma uric acid concentration. Data showed an undetectable value within 1 h of treatment. The rasburicase effect ended after 50 h, with a slow increase in the plasma level of uric acid.
  
  
  CONCLUSIONS
  A single dose of rasburicase is highly effective and well tolerated in the treatment of hyperuricemia in selected CKD patients.
authors.affiliation: Department of Nephrology, Dialysis and Hypertension, Malpighi Hospital, Bologna, Italy. e.sestigiani@aosp.bo.it
authors.forename: E
authors.initials: E
authors.lastname: Sestigiani
authors.forename: M
authors.initials: M
authors.lastname: Mandreoli
authors.forename: M
authors.initials: M
authors.lastname: Guardigli
authors.forename: A
authors.initials: A
authors.lastname: Roda
authors.forename: E
authors.initials: E
authors.lastname: Ramazzotti
authors.forename: P
authors.initials: P
authors.lastname: Boni
authors.forename: A
authors.initials: A
authors.lastname: Santoro
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D033461:Hyperuricemia / Q000188:drug therapy* / Q000209:etiology; D007262:Infusions, Intravenous; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000378:metabolism; D007677:Kidney Function Tests; D008163:Luminescent Measurements / Q000379:methods; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D014503:Urate Oxidase / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014527:Uric Acid / Q000097:blood* / Q000378:metabolism / Q000652:urine
chemical_list: D011994:Recombinant Proteins; C469709:rasburicase; D014527:Uric Acid; D014503:Urate Oxidase