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Aspirin alters methotrexate disposition in rheumatoid arthritis patients

C F Stewart1, R A Fleming, B F Germain

  • 1Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee, Memphis 38163.

Arthritis and Rheumatism
|December 1, 1991
PubMed

Insights

Concomitant aspirin therapy alters methotrexate clearance in rheumatoid arthritis patients. Aspirin reduces methotrexate clearance and increases its unbound fraction without causing acute toxicity.

Area of Science:

  • Pharmacology
  • Rheumatology
  • Clinical Medicine

Background:

  • Rheumatoid arthritis (RA) is a chronic autoimmune disease.
  • Methotrexate (MTX) is a cornerstone therapy for RA.
  • Drug interactions can affect MTX efficacy and safety.

Purpose of the Study:

  • To investigate the effect of concomitant aspirin (ASA) on the pharmacokinetics of intravenous methotrexate (MTX) in RA patients.
  • To assess the safety of combined MTX and ASA therapy.

Main Methods:

  • 15 RA patients received intravenous MTX (10 mg) alone or with oral ASA (3,900 mg/day).
  • Systemic and renal clearance of MTX were measured.
  • Unbound fraction of MTX was determined.
  • Hematologic, renal, and hepatic function were monitored for toxicity.

Main Results:

  • Concomitant ASA administration significantly reduced systemic and renal clearance of MTX.
  • The unbound fraction of MTX was higher when co-administered with ASA.
  • No acute hematologic, renal, or hepatic toxicity was observed with either treatment regimen.

Conclusions:

  • Aspirin acutely alters the clearance of low-dose intravenous methotrexate in RA patients.
  • The combination of low-dose MTX and high-dose ASA did not result in acute toxicity in this cohort.
  • Clinicians should consider potential pharmacokinetic interactions when prescribing concomitant ASA and MTX therapy.

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