Methotrexate Post Glucarpidase, Serum
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Methotrexate, an antimetabolite (folate reductase inhibitor), is used at high dose (12 gm/m) to treat neoplastic diseases, such as lymphocytic leukemia. Therapy is guided by measurement of serum concentration: 24 hours after dosage, the serum concentration should be <10 mcmol/L; 48 hours after therapy, concentration should be <1 mcmol/L; and 72 hours after dosage, the concentration should be <0.1 mcmol/L or <0.05 mcmol/L, depending on clinical protocol. It is also administered at low dose (a single dose of 5-15 mg per week) to treat severe psoriasis and rheumatoid arthritis. Methotrexate is 65% orally bioavailable. Peak serum concentrations are reached 2 to 3 hours after dosing. Protein binding is approximately 45%. Volume of distribution is 0.4 L/kg. Elimination is concentration dependent with an apparent elimination half-life of 1.8 hours when the serum concentration is >1 mcmol/L, 8 hours when between 0.1 and 1 mcmol/L, and approximately 30 hours when <0.1 mcmol/L.
Voraxaze (glucarpidase) is a carboxypeptidase enzyme indicated for the treatment of toxic plasma methotrexate (MTX) concentrations (>1 mcmol/L) in patients with delayed methotrexate clearance due to impaired renal function. Measurement of methotrexate using immunoassays is unreliable for specimens collected within 48 hours following Voraxaze administration since it can result in falsely elevated results. As a result, this liquid chromatography-tandem mass spectrometry assay should be used to monitor MTX concentrations postglucarpidase therapy.
Monitoring methotrexate concentrations postglucarpidase therapy
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.
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