Clinical Information

Methotrexate (MTX) is a folate antimetabolite that reversibly inhibits dihydrofolate reductase. MTX is used alone or in combination with other agents to treat a variety of cancers (ie, breast, leukemia, lymphoma, head and neck, lung, and sarcomas). Administration of intravenous high-dose MTX (ie, 1-15 g/m[2]) occurs at different intervals in treatments and depends on the regimen being used. Therapy is guided by measurement of serum concentration: 24 hours after dosage, the serum concentration should be less than 10 mcmol/L; 48 hours after therapy, concentration should be less than 1 mcmol/L; and 72 hours after dosage, the concentration should be less than 0.1 mcmol/L or less than 0.05 mcmol/L, depending on clinical protocol. MTX can also be used at lower doses (ie, a single dose of 5-15 mg/wk) to treat patients with rheumatoid arthritis and severe psoriasis. In adults, oral absorption appears to be dose dependent. Peak serum concentrations are reached within 1 to 3 hours after oral dosing and 0.5 to 1 hour after intramuscular injection. Protein binding is approximately 50%. Volume of distribution is 0.4 to 0.8 L/kg. Elimination is concentration dependent with an apparent elimination half-life of 3 to 10 hours for patients on low dose therapy (<30 mg/m[2]) compared to 8 to 15 hours for patients on high doses of MTX.