Comparative study on the pharmacokinetics of 7‐hydroxy‐methotrexate after administration of methotrexate in the dose range of 0.5‐33.6 g/m 2 to children with acute lymphoblastic leukemia

Concentrations of 7 ‐hydroxy‐methotrexate ( 7 ‐OH‐MTX) were determined in serum samples obtained after 266 infusions of methotrexate administered to 58 children with acute lymphoblastic leukemia. The dose of methotrexate (MTX) was in the range of 0.5‐33.6 g/m 2 . Pharmacokinetic parameters (metabolic index, drug/metabolite ratio, half‐life) of 7 ‐OH‐MTX and their relationship to the kinetics of methotrexate were analyzed. A great variability was observed in the extent and time‐course of the metabolite formation. The concentration of the metabolite was higher than that of the parent compound at any examined time after the end of the 24 hours' infusion. The increase of 7 ‐OH‐MTX levels at the end of the methotrexate infusion was found to be proportionate to the increase of the dose of MTX. Males had significantly higher metabolite levels than did females ( P