Rational use of methotrexate in maintenance therapy of childhood acute lymphoblastic leukemia.

This study was undertaken to research the pharmacokinetics and bioavailability of methotrexate (MTX). Plasma concentrations were measured by fluorescent spectrometry in 20 normal SD rats, and 28 measurements were done in children with acute lymphoblastic leukemia (ALL). Both rats and children were divided into four groups. Either 20 mg/m2 or 40 mg/m2 of MTX was given IV or PO in each group. The plasma MTX concentrations were measured within 8 hours after administration. The concentration versus time curves were fitted by MCPKP program for pharmacokinetics (PK) and the parameters calculated. After PO administration, the peak concentration, duration of therapeutic concentration and bioavailability were much lower than that after IV administration. The differences were more obvious at 40 mg/m2 dosage. The higher the PO dosage, the lower the bioavailability. Absorption of PO MTX in children with ALL varied widely and uniform concentration was not expected even after equal dosage. Drug concentration was not necessarily increased with dosage. It is our conclusion that drug concentrations and PK parameters should be measured in patients receiving PO MTX therapy.