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High-dose methotrexate: Preliminary evaluation of a pharmacokinetic approach

  • Original Articles
  • High Dose Methotrexate Pharmacokinetics
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Summary

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.

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Authors and Affiliations

  1. Institut Paoli-Calmettes, 232 Bd de Sainte-Marguerite, Marseille, Cedex 2, France

    S. Monjanel, J. P. Cano, Y. Carcassonne & R. Favre

  2. Ecole des Mines, Valbonne, France

    J. P. Rigault

Authors
  1. S. Monjanel
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  2. J. P. Rigault
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  3. J. P. Cano
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  4. Y. Carcassonne
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  5. R. Favre
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with the technical collaboration of F. Baratier

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Monjanel, S., Rigault, J.P., Cano, J.P. et al. High-dose methotrexate: Preliminary evaluation of a pharmacokinetic approach. Cancer Chemother. Pharmacol. 3, 189–196 (1979). https://doi.org/10.1007/BF00262421

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  • DOI: https://doi.org/10.1007/BF00262421

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