Methotrexate metabolism analysis in blood and liver of rheumatoid arthritis patients: Association with hepatic folate deficiency and formation of polyglutamates

Authors

  • Joel M. Kremer MD,

    Corresponding author
    1. Division of Rheumatology, Albany Medical College, Albany, New York
    2. Wadsworth Center for Laboratories and Research, New York State
    3. Department of Health, Albany, New York
    4. Department of Pediatrics and Pharmacology, University of Texas, Southwestern Medical School, Dallas
    • Division of Rheumatology, Albany Medical College, Albany, NY 12208
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  • John Galivan PhD,

    1. Division of Rheumatology, Albany Medical College, Albany, New York
    2. Wadsworth Center for Laboratories and Research, New York State
    3. Department of Health, Albany, New York
    4. Department of Pediatrics and Pharmacology, University of Texas, Southwestern Medical School, Dallas
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  • Anita Streckfuss BS,

    1. Division of Rheumatology, Albany Medical College, Albany, New York
    2. Wadsworth Center for Laboratories and Research, New York State
    3. Department of Health, Albany, New York
    4. Department of Pediatrics and Pharmacology, University of Texas, Southwestern Medical School, Dallas
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  • Barton Kamen MD, PhD

    Scholar of the Leukemia Society of America
    1. Division of Rheumatology, Albany Medical College, Albany, New York
    2. Wadsworth Center for Laboratories and Research, New York State
    3. Department of Health, Albany, New York
    4. Department of Pediatrics and Pharmacology, University of Texas, Southwestern Medical School, Dallas
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Abstract

Serum and red blood cell methotrexate (MTX) levels, as well as hepatic levels of MTX and folate, were analyzed in 24 patients who had received long-term oral MTX weekly for the treatment of rheumatoid arthritis. The serum MTX level peaked rapidly and was insignificant after 24 hours. The red blood cell MTX level was not related to the interval from the last MTX dose. In hepatic tissue obtained by liver biopsy, MTX was found in a predominantly polyglutamated form with depleted hepatic folate stores when compared with baseline specimens. A brief period of therapy with oral folinic acid repleted hepatic folate. It is possible that MTX hepatotoxicity is related to reduced hepatic folate levels and formation of MTX polyglutamates.

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