Evaluation of 24-hour infusion of high-dose methotrexate--pharmacokinetics and toxicity

High-dose methotrexate was administered by constant infusion over 24 h to children with various malignancies. Citrovorum factor was given at the completion of methotrexate infusion and continued for 72 h. Serum concentration of 10(-4) M could be sustained for 24 h with doses of methotrexate over 100 mg/kg. This infusion regimen was well tolerated and only mild neutropenia and mouth sores were seen in most patients. Severe toxicity was seen in one patient and was related to prolonged retention of methotrexate in the circulation. Careful monitoring of serum drug level is mandatory in the use of any high-dose methotrexate regimen.