High-dose methotrexate: preliminary evaluation of a pharmacokinetic approach.
Clinical pharmacologic studies have been carried out in patients with head and neck tumors following 36-h continuous infusions of high-dose MTX (1.5 g/m2). The results indicated considerable variation in the amount of MTX in the blood of individual patients. To control these variations, a modified protocol was set up to try to attain the same MTX blood level in all subjects. The protocol has a pharmacokinetic basis and involves determination of the MTX kinetics in each patient. The information thus obtained allows us to compute a 36-h infusion dose so that the MTX plasma levels never exceed a threshold beyond which there is a risk of toxicity to the host. The computation is validated by taking a blood sample 6 h after the beginning of the infusion. If the MTX concentration is higher than its expected value, the infusion rate can then be immediately reduced. Analytical methods that will allow such a computation, the results of the clinical application of this pharmacokinetic approach, and some implications of such a method are discussed.
D000368:Aged; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D007263:Infusions, Parenteral; D007700:Kinetics; D008727:Methotrexate / Q000008:administration & dosage* / Q000378:metabolism / Q000627:therapeutic use; D008875:Middle Aged; D008954:Models, Biological
D008727:Methotrexate