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  • Title: [Pharmacokinetics of methotrexate in rheumatoid arthritis: therapeutic implications].
    Author: Bannwarth B, Péhourcq F, Lequen L.
    Journal: Therapie; 1997; 52(2):129-32. PubMed ID: 9231507.
    Abstract:
    The fraction of oral methotrexate (MTX) absorbed averages 70 per cent at low doses (< or = 10 mg/m2), both fasting and after food. The mean binding of MTX to serum albumin is 42-57 per cent. Less than 10 per cent of MTX is oxidised to 7-OH-MTX. Furthermore, MTX is partly converted to polyglutamate derivatives which accumulate in some cells resulting in sustained efficacy of the drug in spite of its relatively short plasma elimination half-life. MTX is mainly excreted by the kidney as intact drug. Accordingly careful monitoring of renal function is justified. MTX undergoes bidirectional transport within the renal tubules leading to drug interactions. Oral, intramuscular and subcutaneous routes of administration were reported to result in comparable bioavailability. There is a marked interindividual variability in MTX disposition. Conversely, the intraindividual variability is moderate even over a long time period. Finally, no clear relationship between pharmacokinetic parameters and clinical response or toxicity has been found in patients with rheumatoid arthritis.
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