The effects of a salicylate, ibuprofen, and naproxen on the disposition of methotrexate in patients with rheumatoid arthritis

Eur J Clin Pharmacol. 1992;42(2):121-5. doi: 10.1007/BF00278469.


We have studied the pharmacokinetics of methotrexate in patients with rheumatoid arthritis concurrently treated with choline magnesium trisalicylate, ibuprofen, naproxen, or a non-NSAID analgesic (control treatment). The apparent systemic clearance of methotrexate was significantly reduced by all three treatments. Trisalicylate and ibuprofen both significantly reduced methotrexate renal clearance, but only the trisalicylate significantly displaced methotrexate from protein, increasing the fraction unbound by 28%. These data show that NSAIDs can affect the disposition of methotrexate, possibly increasing the potential for toxicity and necessitating dosage adjustments. However, large inter-subject variability precludes specific dosage recommendations.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Arthritis, Rheumatoid / metabolism*
  • Blood Proteins / metabolism
  • Choline / administration & dosage
  • Choline / analogs & derivatives*
  • Choline / therapeutic use
  • Female
  • Humans
  • Ibuprofen / therapeutic use*
  • Kidney / metabolism
  • Male
  • Metabolic Clearance Rate
  • Methotrexate / pharmacokinetics*
  • Middle Aged
  • Naproxen / therapeutic use*
  • Protein Binding
  • Salicylates / administration & dosage
  • Salicylates / therapeutic use*


  • Anti-Inflammatory Agents, Non-Steroidal
  • Blood Proteins
  • Salicylates
  • Naproxen
  • choline magnesium trisalicylate
  • Choline
  • Ibuprofen
  • Methotrexate