PMID: 6976674Sep 1, 1981Paper

Methotrexate in the plasma and cerebrospinal fluid of children treated with intermediate dose methotrexate

Acta paediatrica Scandinavica
C RechnitzerJ Hendel

Abstract

Serious complications can follow treatment with intermediate dose methotrexate of acute lymphoblastic leukemia in childhood. Toxicity has been shown to be correlated to plasma methotrexate concentrations. During intravenous infusions of methotrexate (500 mg/m2) the mean concentrations achieved 1 to 41/2 hours after the start of infusion were 1.3 X 10(-7) mol/l in cerebrospinal fluid and 1.7 X 10(-5) mol/l in plasma. At 72 hours after start of methotrexate infusion, plasma methotrexate concentrations were significantly higher in cases with symptoms of toxicity. In all the children who developed toxic symptoms 72-hour plasma methotrexate concentration was above 1 X 10(-7) mol/l. Assuming that leucovorin is given 48 hours after the start of methotrexate infusion, 72-hour plasma methotrexate is suitable for detection of patients at risk for toxicity. In children treated with intermediate dose methotrexate we therefore recommend estimating plasma methotrexate concentration 72 hours after the start of infusion, and instituting supplementary leucovorin when plasma methotrexate concentration exceeds 1 X 10(-7) mol/l.

References

May 1, 1978·Acta paediatrica Scandinavica·P J Moe, M Seip
Sep 22, 1977·The New England Journal of Medicine·R G StollerB A Chabner
Nov 16, 1978·European Journal of Clinical Pharmacology·D Bratlid, P J Moe
Nov 1, 1969·The Journal of Clinical Investigation·W M Hryniuk, J R Bertino

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