Pharmacokinetic and clinical studies of 24-h infusions of high-dose methotrexate.
Cytocidal activity of a drug is dependent on both drug dosage and duration of exposure. In contrast to the 'conventional" 6-h infusion and in an attempto to improve its efficacy, the high-dose methotrexate therapeutic regimen was given over a 24-h period with 10% of the dose administered in the first hour. Citrovorum factor was initiated at hour 24 and continued for 72 h. Treatment was administered every 2-3 weeks. 57 infusions were performed in twelve patients aged 7-20 years (six with osteogenic sarcoma and six with acute lymphoblastic leukemia). Determinations of serum methotrexate levels revealed that the levels were dependent on the dose. Levels assayed at 24 h revealed the following results: 4.4 +/- 1.4 x 10(-5) molar with 4.5 g/m(2), 2.04 +/- 0.34 x 10(-4) molar with 7.5 g/m(2) and 4.59 +/- 0.80 x 10(-4) molar with 12.5 g/m(2). Major toxicity was myelosuppression in 12 of 57 patients. There were no responses. The study demonstrates that 24-h infusions of high-dose methotrexate can be tolerated every 2-3 weeks in patients without bone marrow involvement and levels of at least 10(-4) molar can be maintained during the infusion.
D000293:Adolescent; D000328:Adult; D002648:Child; D002986:Clinical Trials as Topic; D006801:Humans; D007263:Infusions, Parenteral; D007700:Kinetics; D002955:Leucovorin / Q000627:therapeutic use; D007945:Leukemia, Lymphoid / Q000188:drug therapy*; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D012516:Osteosarcoma / Q000188:drug therapy*; D013997:Time Factors
D002955:Leucovorin; D008727:Methotrexate