7-hydroxymethotrexate and Carcinoma--Squamous-Cell

Plasma concentrations of 7-hydroxymethotrexate were measured in 10 individuals receiving methotrexate, 8 of them per infusion. After the end of infusion, the plasma concentration of formed 7-hydroxymethotrexate fell less rapidly than that of methotrexate. At 24 h after infusion, plasma concentration ratios of 7-hydroxymethotrexate ranged from 30 to 1 (n = 8). The presence of 7-hydroxymethotrexate was shown to influence the transport of methotrexate into Ehrlich ascites tumor cells and human KB cells, cultured in vitro. These findings suggest that monitoring of 7-OHMTX is important in MTX treatment.

Topics: Animals; Biological Transport; Carcinoma, Ehrlich Tumor; Carcinoma, Squamous Cell; Cells, Cultured; Folic Acid Antagonists; Half-Life; Humans; Hydroxylation; Infusions, Parenteral; Injections, Intravenous; Methotrexate; Neoplasms

Human subjects and rhesus monkeys receiving the antitumor agent methotrexate at the high dose levels recently introduced into clinical use (greater than 50 mg/kg) excrete significant amounts of the metabolite 7-hydroxymethotrexate. The metabolite is not detected in these species after methotrexate therapy at conventional dose levels. The evidence indicates that in primates, the in vivo conversion of methotrexate to 7-hydroxymethotrexate is a dose-dependent phenomenon, with the enzyme system(s) catalyzing the reaction having a low affinity for the drug.

Topics: Adult; Animals; Bone Neoplasms; Carcinoma, Squamous Cell; Child; Female; Histocytochemistry; Humans; Kidney; Lung Neoplasms; Macaca mulatta; Male; Methotrexate; Middle Aged; Osteosarcoma; Time Factors