Degradation and clearance of methotrexate in children with osteosarcoma receiving high-dose infusion

Abstract

Plasma methotrexate (MTX) concentrations were quantitated in 34 patients after 127 high-dose (35--350 mg/kg) infusions with citrovorum factor rescue. Significant linear correlations have been obtained between methotrexate dosage and concentrations in plasma at 6 and 24 hours after the initiation of the therapy. However, similar trends have not been observed when 48- and 72-hour samples were analyzed. Clinical toxicity was not serious when the methotrexate level in plasma was less than 4.5 X 10(-6) M at 48 hours after the start of a six-hour infusion in children. A minimal four-hour steady-state methotrexate plasma level can be maintained during a six-hour infusion. Children excrete methotrexate at a faster rate than adults; the half-life of MTX during the first phase of plasma clearance curve is one hour shorter in children. Urinary analyses have indicated that substantial methotrexate is metabolized. The chemical nature of these components has not been identified. Further, the urinary metabolic profiles varied among patients.