Effect of etodolac on methotrexate pharmacokinetics in patients with rheumatoid arthritis.

Objective. To determine if the pharmacokinetics of methotrexate (MTX) is modified by the coadministration of etodolac. Methods. MTX (10 mg) was administered intramuscularly in the absence and presence of steady state levels of etodolac in 19 patients with rheumatoid arthritis. MTX levels were assayed by fluorescence polarization immunoassay. Concentrations of 7-hydroxymethotrexate (7-OH-MTX) were assayed by a reverse phase high performance liquid chromatography method. The unbound fraction was determined by ultrafiltration. Results. When etodolac was coadministered with MTX, the highest observed concentration decreased and the mean residence time increased to become statistically significant