Influence of concomitant aspirin or prednisone on methotrexate synovial fluid concentration

Methotrexate (MTX) is currently being used in the treatment of patients with rheumatoid arthritis. The purpose of this study was to investigate the effect of two classes of drugs, steroids and salicylates, on MTX synovial fluid concentrations. A novel canine model of monoarticular inflammation was used, in which each animal served as its own control with both inflamed and normal knees in the same animal. After the 6-week immunization process, animals in each group received either no drug (control), prednisone or aspirin (low dose and high dose) for 1 week before MTX. On the day of the study, each animal was given i.v. MTX, and serial serum and synovial fluid samples were obtained. Laboratory, histologic and clinical observations supported the presence of monoarticular inflammation. The end-of-infusion synovial MTX concentration in inflamed knees was significantly greater than in normal knees (P less than .05), but, 2 hr after the end of infusion, they were not different. The end-of-infusion ratio of synovial fluid MTX concentration to serum MTX concentration (both total and unbound) was significantly lower in the prednisone group than in the other treatment groups (P less than .05). The end-of-infusion ratio of the MTX synovial concentration in the inflamed knee compared with the normal knee at 2 hr was significantly lower in the prednisone group than in the other three treatment groups (P less than .05). These results have therapeutic implications for the use of MTX in treating rheumatoid arthritis.