title: Effect of allopurinol versus urate oxidase on methotrexate pharmacokinetics in children with newly diagnosed acute lymphoblastic leukemia.
abstract: BACKGROUND
  Allopurinol and urate oxidase are both effective in preventing or treating hyperuricemia during remission induction therapy for lymphoid malignancies, but to the authors' knowledge, their effects on concomitant anticancer drug therapy have not been compared.
  
  
  METHODS
  The authors compared plasma methotrexate pharmacokinetics in pediatric patients with newly diagnosed acute lymphoblastic leukemia who received concomitant allopurinol (n = 20) versus those treated with nonrecombinant or recombinant urate oxidase (n = 96) during high-dose methotrexate administration before conventional remission induction therapy.
  
  
  RESULTS
  The minimum plasma concentration of uric acid was significantly (P < .0001) lower after urate oxidase treatment than the concentration after allopurinol treatment. Methotrexate clearance was significantly higher (median, 117.1 mL/minute/m(2) vs 91.1 mL/minute/m(2); P = .019) in patients who received urate oxidase. A higher proportion of patients in the allopurinol group had elevated methotrexate plasma concentrations (36% vs 7%; P = .003) and experienced mucositis (45% vs 16%; P = .003) after methotrexate treatment compared with the urate oxidase group.
  
  
  CONCLUSIONS
  The lower rate of methotrexate clearance in patients who received allopurinol likely reflected a less potent hypouricemic effect of allopurinol, leading to precipitation of uric acid in renal tubules. Hence, during remission induction therapy for lymphoid malignancies, the authors concluded that renally excreted drugs should be monitored closely, especially in patients who are receiving allopurinol.
authors.affiliation: Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN 38105-3678, USA. kristine.crews@stjude.org
authors.forename: Kristine R
authors.initials: KR
authors.lastname: Crews
authors.forename: Yinmei
authors.initials: Y
authors.lastname: Zhou
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Pauley
authors.forename: Scott C
authors.initials: SC
authors.lastname: Howard
authors.forename: Sima
authors.initials: S
authors.lastname: Jeha
authors.forename: Mary V
authors.initials: MV
authors.lastname: Relling
authors.forename: Ching-Hon
authors.initials: CH
authors.lastname: Pui
mesh_terms: D000493:Allopurinol / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D033461:Hyperuricemia / Q000517:prevention & control; D007223:Infant; D008297:Male; D008727:Methotrexate / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy; D014503:Urate Oxidase / Q000494:pharmacology*; D014527:Uric Acid / Q000097:blood
chemical_list: D014527:Uric Acid; D000493:Allopurinol; D014503:Urate Oxidase; D008727:Methotrexate