Effect of allopurinol versus urate oxidase on methotrexate pharmacokinetics in children with newly diagnosed acute lymphoblastic leukemia

Kristine R. Crews, Yinmei Zhou, Jennifer L. Pauley, Scott Howard, Sima Jeha, Mary V. Relling, Ching Hon Pui

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)227-232
Number of pages6
JournalCancer
Volume116
Issue number1
DOIs
StatePublished - Jan 1 2010

Fingerprint

Urate Oxidase
Allopurinol
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Methotrexate
Pharmacokinetics
Remission Induction
Uric Acid
Therapeutics
Hyperuricemia
Mucositis
Neoplasms
Pediatrics
Kidney
Drug Therapy

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Effect of allopurinol versus urate oxidase on methotrexate pharmacokinetics in children with newly diagnosed acute lymphoblastic leukemia. / Crews, Kristine R.; Zhou, Yinmei; Pauley, Jennifer L.; Howard, Scott; Jeha, Sima; Relling, Mary V.; Pui, Ching Hon.

In: Cancer, Vol. 116, No. 1, 01.01.2010, p. 227-232.

Research output: Contribution to journalArticle

Crews, Kristine R. ; Zhou, Yinmei ; Pauley, Jennifer L. ; Howard, Scott ; Jeha, Sima ; Relling, Mary V. ; Pui, Ching Hon. / Effect of allopurinol versus urate oxidase on methotrexate pharmacokinetics in children with newly diagnosed acute lymphoblastic leukemia. In: Cancer. 2010 ; Vol. 116, No. 1. pp. 227-232.
@article{a52e93a47ca6479fa4c68432e63610af,
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.",
author = "Crews, {Kristine R.} and Yinmei Zhou and Pauley, {Jennifer L.} and Scott Howard and Sima Jeha and Relling, {Mary V.} and Pui, {Ching Hon}",
year = "2010",
month = "1",
day = "1",
doi = "10.1002/cncr.24681",
language = "English (US)",
volume = "116",
pages = "227--232",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "1",

}

TY - JOUR

T1 - Effect of allopurinol versus urate oxidase on methotrexate pharmacokinetics in children with newly diagnosed acute lymphoblastic leukemia

AU - Crews, Kristine R.

AU - Zhou, Yinmei

AU - Pauley, Jennifer L.

AU - Howard, Scott

AU - Jeha, Sima

AU - Relling, Mary V.

AU - Pui, Ching Hon

PY - 2010/1/1

Y1 - 2010/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=74549175655&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=74549175655&partnerID=8YFLogxK

U2 - 10.1002/cncr.24681

DO - 10.1002/cncr.24681

M3 - Article

C2 - 19834958

AN - SCOPUS:74549175655

VL - 116

SP - 227

EP - 232

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 1

ER -