Kinetics of 7-hydroxy-methotrexate after high-dose methotrexate therapy.
Kinetics of 7-hydroxy-methotrexate (7-OH-MTX) excretion after high-dose methotrexate (MTX) (12 g/m2) therapy were monitored in 93 consecutive drug cycles of 19 adolescent patients with osteosarcoma. A reversed-phase HPLC method was used. Serum elimination was found to be monophasic with a mean half-life of 5.5 h. Shortly after the 4-h MTX infusion period 7-OH-MTX levels exceeded those of the parent compound. By 12 h after MTX infusion 7-OH-MTX levels were 16.5 times higher than those of MTX itself. Autostimulation of MTX metabolism leading to enhanced 7-OH-MTX production after repeated drug cycles was not observed. The production of 7-OH-MTX decreased significantly from the first to the last high-dose MTX cycle of the adjuvant chemotherapy protocol.
D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D002648:Child; D006801:Humans; D007700:Kinetics; D002955:Leucovorin / Q000008:administration & dosage; D008727:Methotrexate / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D012516:Osteosarcoma / Q000188:drug therapy; D012189:Retrospective Studies
D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D002955:Leucovorin; C011864:7-hydroxymethotrexate; D008727:Methotrexate