Mathematical modeling -- guide to high-dose methotrexate infusion therapy.

A mathematical model that describes methotrexate pharmacokinetics has been refined for use as a guide to dose escalation during high-dose methotrexate infusion therapy. Parameters for the model are adjusted for a patients by the SAAM computer program of Berman and Weiss, on the basis of plasma concentrations obtained during the initial course of therapy. Various dose escalations can be simulated by the computer and a print-out of predicted plasma concentrations obtains. The model has been used successfully to predict plasma concentrations after high-dose infusions in patients, including those with abnormal creatinine clearances. The program is designed to allow comparisons among infusions of any duration. This can be helpful when a change from a 24-hour infusion to a 6-hour infusion is contemplated for a patient. Deviations of observed values from those predicted are used to warn of the possibility of delayed toxicity secondary to methotrexate and alert the physician that increased amounts of rescue agent may be required.