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Related Experiment Videos

Methotrexate serum binding in rheumatoid arthritis

P Claudepierre1, S Urien, X Chevalier

  • 1Laboratoire de Pharmacologie, Faculté de Médecine, Créteil, Université Paris, France.

International Journal of Clinical Pharmacology and Therapeutics
|March 1, 1994
PubMed
Summary

Serum protein binding of methotrexate is primarily to albumin. Conditions like rheumatoid arthritis, cancer, and certain drug interactions can affect this binding, potentially influencing methotrexate toxicity.

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Area of Science:

  • Pharmacology
  • Biochemistry
  • Clinical Medicine

Background:

  • Methotrexate is a widely used chemotherapy and immunosuppressive drug.
  • Understanding its serum protein binding is crucial for predicting its efficacy and toxicity.
  • Albumin is the primary serum protein responsible for binding many drugs, including methotrexate.

Purpose of the Study:

  • To quantify the serum protein binding of methotrexate.
  • To investigate the influence of specific disease states (rheumatoid arthritis, cancer) on methotrexate binding.
  • To assess the impact of common co-administered drugs (salicylate, naproxen) on methotrexate serum binding.

Main Methods:

  • Equilibrium dialysis was employed to determine serum protein binding.
  • Radiolabelled methotrexate was used for accurate quantification.

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  • Binding percentages were compared across control groups and patient cohorts.

    • Main Results:

    • Methotrexate exclusively binds to albumin in serum.
    • Serum binding percentages were similar in controls (46%), rheumatoid arthritis (42%), and cancer (44%).
    • Salicylate and high-dose naproxen significantly reduced methotrexate serum binding.

    Conclusions:

    • Serum albumin is the main binder of methotrexate.
    • Hypoalbuminemia may alter methotrexate pharmacokinetics.
    • Concomitant use of salicylate or high-dose naproxen can decrease methotrexate binding, potentially increasing toxicity risk.