Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Methotrexate is an antineoplastic agent that inhibits the enzyme, dihydrofolate reductase. Such inhibition causes a stoppage of synthesis of tetrahydrofolate that, in turn, results in an inhibition of nucleotide and ultimately of DNA synthesis.
Methotrexate is effective against malignancies with rapid cell proliferation such as acute lymphoblastic leukemia, choriocarcinoma, trophoblastic tumors in women, and carcinomas of the breast, tongue, pharynx, and testis.
When used as an antineoplastic agent against these tumors, methotrexate is administered at high dose (2.5 mg/kg or 3.3 mg/kg), and usually is followed by leucovorin (folinic acid) rescue to salvage nontumor cells.
Following therapy, serum concentration is used to judge whether the drug is being cleared appropriately and verify that a nontoxic level has been attained.
Following a 4 to 6 hour intravenous infusion of methotrexate, postinfusion concentrations greater than the following indicate an increased risk of toxicity if conventional low dose leucovorin rescue is given:
-24-hour postinfusion concentration: 5.0 to 10.0 mcmol/L
-48-hour postinfusion concentration: 0.5 to 1.0 mcmol/L
-72-hour postinfusion concentration: 0.1 mcmol/L
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
The specimen must be protected from light.
Important: Specimens from patients who have received glucarpidase (carboxypeptidase G2) as a high-dose methotrexate rescue therapy should not be tested with this immunoassay. Methotrexate concentrations should be performed using the liquid chromatography-tandem mass spectrometry method to avoid the reporting of falsely elevated methotrexate values due to an interference which could confuse the efforts of the glucarpidase therapy. After glucarpidase therapy, it can take at least 5 to 7 days before accurate measurements of serum methotrexate can be obtained using an immunoassay.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Nontoxic drug concentration after 72 hours: <0.1 mcmol/L
Clinical References Provides recommendations for further in-depth reading of a clinical nature
Cadman EC, Durivage HJ: Cancer chemotherapy: alkylating agents. In Harrison's Principles of Internal Medicine. 12th edition. Edited by JD Wilson, E Braunwald, KJ Isselbacher, et al. New York, McGraw-Hill Book Company, 1991, pp 1592-1594