RATIONAL USE OF METHOTREXATE IN MAINTENANCE THERAPY OF CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA

<正> This study was undertaken to research thepharmacokinetics and bioavailability of methotrexate（MTX）.Plasma concentrations were measured by flu-orescent spectrometry in 20 normal SD rats,and 28measurements were done in children with acutelymphoblastic leukemia（ALL）.Both rats and childrenwere divided into four groups.Either 20 mg/m2 or 40mg/m2 of MTX was given IV or PO in each group.The plasma MTX concentrations were measured with-in 8 hours after administration.The concentration ver-sus time curves were fitted by MCPKP program forphamacokinetics（PK）and the parameters calculated. After PO administration,the peak concentration,duration of therapeutic concentration andbioavailability were much lower than that after IVadiministration.The differences were more obvious at40mg/m2 dosage.The higher the PO dosage,thelower the bioavalability.Absorption of PO MTX inchildren with ALL varied widely and uniform concen-tration was not expected even after equal dosage.Drugconcentration was not necessarily increased withdosage.It is our conclusion that drug concentrationsand PK parameters should be measured in patients re-ceiving PO MTX therapy.