Effect of allopurinol versus urate oxidase on methotrexate pharmacokinetics in children with newly diagnosed acute lymphoblastic leukemia.
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.
Crews
Kristine R
KR
Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN 38105-3678, USA. kristine.crews@stjude.org
Zhou
Yinmei
Y
Pauley
Jennifer L
JL
Howard
Scott C
SC
Jeha
Sima
S
Relling
Mary V
MV
Pui
Ching-Hon
CH
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
D014527:Uric Acid; D000493:Allopurinol; D014503:Urate Oxidase; D008727:Methotrexate