Influence of concomitant aspirin or prednisone on methotrexate synovial fluid concentration

C. F. Stewart, Michael Christensen, R. P. Evens, M. Cremer, W. E. Evans

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Abstract

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 < .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 < .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 < .05). These results have therapeutic implications for the use of MTX in treating rheumatoid arthritis.

Original languageEnglish (US)
Pages (from-to)131-137
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume243
Issue number1
StatePublished - Jan 1 1987

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Synovial Fluid
Prednisone
Methotrexate
Aspirin
Knee
Rheumatoid Arthritis
Inflammation
Salicylates
Drug and Narcotic Control
Therapeutic Uses
Serum
Canidae
Immunization
Therapeutics
Steroids

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

Influence of concomitant aspirin or prednisone on methotrexate synovial fluid concentration. / Stewart, C. F.; Christensen, Michael; Evens, R. P.; Cremer, M.; Evans, W. E.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 243, No. 1, 01.01.1987, p. 131-137.

Research output: Contribution to journalArticle

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abstract = "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 < .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 < .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 < .05). These results have therapeutic implications for the use of MTX in treating rheumatoid arthritis.",
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