AGE-RELATED PHARMACOKINETICS OF HIGH-DOSE METHOTREXATE IN PATIENTS WITH OSTEOSARCOMA

  • 1 January 1979
    • journal article
    • research article
    • Vol. 63  (3) , 405-410
Abstract
Plasma methotrexate (MTX) concentrations were determined in 52 patients after 409 infusions of high-dose (HD) (50-250 mg/kg) MTX with citrovorum factor (CF) rescue. Detailed pharmacokinetic studies were conducted in 9 of these patients. Plasma drug levels were compared at 6, 24, 48 and 72 h from the start of MTX infusions in 4 different age groups (.ltoreq. 10, 11-14, 15-17 and .gtoreq. 18 yr). At the same drug dose, the younger patients had lower plasma MTX levels than the older patients at 6 and 24 h. This difference increased in significance with increasing MTX dose. MTX plasma levels became similar at 48 and 72 h, regardless of age. The half-life for the 1st phase of biphasic MTX clearance in children was shorter than that in adults. The urinary excretion of MTX was faster in younger children at all doses. The younger patients had a greater apparent volume of distribution of MTX after HD infusion. The age-dependent pharmacokinetics can probably be attributed to greater distribution and elimination of MTX in the younger patients. The potential difference in the metabolism of MTX between children and adults is currently under investigation. Age probably exerts a dominant effect on the pharmacokinetics of HD-MTX.

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