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Effect of combination chemotherapy, duration of methotrexate administration, and Patient's age on methotrexate pharmacokinetics

  • Original Articles
  • Methotrexate Pharmacokinetics
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Summary

The kinetics of methotrexate were studied in a group of 59 patients after infusion of high doses. From the triexponential analysis of the serum concentration curve, rate constants and relative concentrations in non-circulating pools were calculated, using a linear ‘mammillary’ three-compartment model. No significant variation as a function of dose (300–6,000 mg/m2) was observed. In circumstances the rapidly exchanging pool was a reflection of the circulating pool, suggesting that it is an extravascular, protein-bound pool of methotrexate. Considerable variations of the relative concentration and rate constants of the slowly exchanging pool were observed to be a function of the duration of methotrexate infusion, the presence of other drugs, and the patient's age. If this compartment is assumed to include the target cells for methotrexate, then the large variations observed could be responsible for individual differences in toxicity and/or effectiveness.

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Author notes

  1. François Lokiec

    Present address: Laboratoire de Pharmacologie-Pharmacocinétique, Centre René Huguenin (Dir. J. Gest), 5, rue Gaston Latouche, 92211, Saint-Cloud, France

Authors and Affiliations

  1. Groupe de Pharmacologie Clinique des anticancéreux, Hôpital Saint-Louis, 2, Place du Dr A. Fournier, F-75010, Paris, France

    François Lokiec, Odette Poirier, Christian Gisselbrecht, Michel Marty, Michel Boiron & Yves Najean

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  1. François Lokiec
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  2. Odette Poirier
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  3. Christian Gisselbrecht
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  4. Michel Marty
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  5. Michel Boiron
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  6. Yves Najean
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Lokiec, F., Poirier, O., Gisselbrecht, C. et al. Effect of combination chemotherapy, duration of methotrexate administration, and Patient's age on methotrexate pharmacokinetics. Cancer Chemother. Pharmacol. 9, 165–168 (1982). https://doi.org/10.1007/BF00257746

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  • DOI: https://doi.org/10.1007/BF00257746

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