Disposition of intermediate-dose methotrexate in children with acute lymphocytic leukemia

W. E. Evans, C. F. Stewart, P. R. Hutson, D. A. Cairnes, Paul Bowman, G. C. Yee, W. R. Crom

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Abstract

Intermediate-dose methotrexate (MTX 200 mg/m2 iv in a bolus dose, followed by 800 mg/m2 iv, infused over 24 hours) is being used as a component of therapy for children with acute lymphocytic leukemia. To define the extent of interpatient variability in MTX disposition, with this dosage and schedule, the systemic clearance of MTX was measured in 69 children (total doses, 717; median, 10 doses per patient). The mean (± SD) systemic clearance was 91.6 (± 25.2) ml/min/m2 and ranged from 50-161 ml/min/m2. Renal clearance was measured in 16 of these patients and averaged 50.7 (± 14) ml/min/m2 during the MTX infusion (0-24 h), at which time mean systemic clearance was 8.7 (±19) and nonrenal clearance was 31.1 (± 11.8) ml/min/m2. Measurement of 7-hydroxy-methotrexate in serum and urine was consistent with the substantial amount of nonrenal (metabolic) clearance observed in these patients. Cerebrospinal fluid MTX concentrations, measured at 24 hours, were 0.26 (± 0.1) μM when only the intravenous MTX was given and 1.08 (± 0.8) μM when an intrathecal dose (12 mg/m2) was also given at the start of the 24-hour infusion. This study establishes that there is substantial interpatient variability in MTX disposition in children and suggests a possible cause of variable patient response to MTX.

Original languageEnglish
Pages (from-to)839-842
Number of pages4
JournalUnknown Journal
Volume16
Issue number11
DOIs
StatePublished - 1 Jan 1982

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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Methotrexate
Cerebrospinal Fluid
Appointments and Schedules
Urine
Kidney
Serum
Therapeutics

Cite this

Evans, W. E., Stewart, C. F., Hutson, P. R., Cairnes, D. A., Bowman, P., Yee, G. C., & Crom, W. R. (1982). Disposition of intermediate-dose methotrexate in children with acute lymphocytic leukemia. Unknown Journal, 16(11), 839-842. https://doi.org/10.1177/106002808201601105
Evans, W. E. ; Stewart, C. F. ; Hutson, P. R. ; Cairnes, D. A. ; Bowman, Paul ; Yee, G. C. ; Crom, W. R. / Disposition of intermediate-dose methotrexate in children with acute lymphocytic leukemia. In: Unknown Journal. 1982 ; Vol. 16, No. 11. pp. 839-842.
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Evans, WE, Stewart, CF, Hutson, PR, Cairnes, DA, Bowman, P, Yee, GC & Crom, WR 1982, 'Disposition of intermediate-dose methotrexate in children with acute lymphocytic leukemia', Unknown Journal, vol. 16, no. 11, pp. 839-842. https://doi.org/10.1177/106002808201601105

Disposition of intermediate-dose methotrexate in children with acute lymphocytic leukemia. / Evans, W. E.; Stewart, C. F.; Hutson, P. R.; Cairnes, D. A.; Bowman, Paul; Yee, G. C.; Crom, W. R.

In: Unknown Journal, Vol. 16, No. 11, 01.01.1982, p. 839-842.

Research output: Contribution to journalArticle

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AU - Evans, W. E.

AU - Stewart, C. F.

AU - Hutson, P. R.

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AU - Yee, G. C.

AU - Crom, W. R.

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