title: Pharmacokinetics of methotrexate and 7-hydroxy-methotrexate after methotrexate infusions.
abstract: Methotrexate was administered by IV infusion, 2g (1.19 +/- 0.05 g/m2) over 24 hours, to a homogeneous group of patients undergoing treatment for breast cancer. Three courses were given at three week intervals. Methotrexate and 7-hydroxy-methotrexate plasma and urine pharmacokinetics were investigated. The average terminal half-lives of methotrexate and 7-hydroxy-methotrexate in plasma were 15.02 and 15.19 hours respectively. The area under concentration-time curve was 723.8 +/- 196.4 microM x h for methotrexate and 598.1 +/- 212.5 microM x h for 7-hydroxy-methotrexate. The total average urinary excretions of methotrexate and 7-hydroxy-methotrexate over a 96 hour period were 52% and 5.4% respectively. Urinary clearance of methotrexate was 3.46 +/- 1.4 1/h. In contrast, urinary excretion of 7-hydroxy-methotrexate was not linear. These results confirm the protein binding of metabolite to serum albumin and may suggest that distribution of 7-hydroxy-methotrexate is different from unchanged drug or that the metabolite can be eliminated by another route, such as bile.
mesh_terms: D000368:Aged; D001711:Biotransformation; D001943:Breast Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000627:therapeutic use; D008727:Methotrexate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008875:Middle Aged
chemical_list: D002955:Leucovorin; C011864:7-hydroxymethotrexate; D008727:Methotrexate