The effects of non-steroidal anti-inflammatory drugs on the disposition of methotrexate in patients with rheumatoid arthritis.

We have studied the pharmacokinetics of methotrexate in patients with rheumatoid arthritis concurrently taking the most commonly used non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, diclofenac, naproxen, indomethacin, and ibuprofen. The area under the curve, the total systemic clearance, the distribution volume, and the half-life of methotrexate in patients receiving concurrent NSAID therapy did not change significantly (at p < 0.05). Concurrent treatment with NSAIDs resulted in increased inter-patient variability of methotrexate concentration, possibly as a result of biochemical interactions; however, it does not appear clinically relevant. The data suggest that the NSAIDs do not significantly affect the disposition of methotrexate, contrary to some of the earlier reports.