Methotrexate in blood, urine, and cerebrospinal fluid of children receiving high doses by infusion.

Abstract

Methotrexate was determined in plasma (31 patients), urine (eight patients), and cerebrospinal fluid (two patients) after high doses (35 to 150 mg/kg) by infusion, with citrovorum factor rescue. Concentrations in plasma were proportional to dose at 6, 24, 72 h after beginning treatment, but this trend was very minimal for samples obtained at 48 h. Clinical toxicity probably will not be serious if the methotrexate concentration in the serum is less than 4.5 X 10(-6) mol/liter at 48 h after the start of a 6-h infusion. In both of the two patients so examined, therapeutic concentrations appeared in cerebrospinal fluid after intravenous infusion of the drug. A kinetic enzymic method, radioassay, and radioimmunoassay all yielded similar results for drug concentrations.