The effects of three non-steroidal anti-inflammatory drugs (NSAIDs) on the pharmacokinetics of methotrexate were studied in 10 patients with rheumatoid arthritis.Ketoprofen (3 mg kg-' day-'), flurbiprofen (3 mg kg-' day-'), piroxicam (20 mg day-') or a non-NSAID control (paracetamol/acetaminophen) were administered to patients for at least 6 days (13 days in the case of piroxicam to establish steady state) in a randomized crossover design prior to receiving a weekly oral dose of methotrexate. In the non-NSAID control portion of the study, MTX oral clearance (CLo) was 11.0 ± 3.9 1 h-', renal clearance (CLR) was 7.9 ± 2.8 1 h-1, percent