title: Pharmacokinetics of low-dose methotrexate in children receiving maintenance therapy for acute lymphoblastic leukaemia.
abstract: Serum methotrexate (MTX) concentrations were measured by immunoassay in 28 children receiving maintenance therapy for acute lymphoblastic leukaemia. Patients were studied either after a single weekly dose or on the first day of a 5-day course of treatment. A standard dose (15 mg/m2) was given PO and/or IV. After PO dose the peak serum MTX concentration and its timing varied widely between cases and there was a significant positive correlation between the rate of serum concentration rise and the area under the concentration curve up to 4 h. The absorption rate constant showed a biphasic distribution and correlated less closely with early serum concentrations. After IV and PO administration drug disposition was triphasic with an initial rapid distribution phase, an intermediate phase, and a prolonged terminal elimination phase. The intermediate phase half-life was significantly longer after PO than after an IV dose. The MTX clearance rate was consistently lower than the glomerular filtration rate and there was no significant correlation between the two. The mean bioavailability (PO/IV) was 42%, but bioavailability was as low as 6% in some cases due to prolonged high serum concentrations after an IV dose, which was not seen with the equivalent PO dose.
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007275:Injections, Intravenous; D007700:Kinetics; D007945:Leukemia, Lymphoid / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008727:Methotrexate / Q000378:metabolism* / Q000627:therapeutic use
chemical_list: D008727:Methotrexate