Simultaneous pharmacokinetics of indomethacin in serum and synovial fluid.

Much evidence has been presented to support the concept that the proliferative and destructive changes of rheumatoid arthritis (RA) are related to synovial immune complex deposition with subsequent release of injurious leucocyte lysosomal enzymes into the synovial membrane and synovial fluid (Zvaifler, 1970). The evidence for a local pathogenic process within the rheumatoid joint, coupled with the pharmacological principle that the efficacy of most therapeutic agents is related to serum drug concentrations and especially to drug concentration at the target receptor cells (Rosenoer and Gill, 1972; Koch-Weser, 1972), suggests that the measurement of synovial fluid drug levels might help to establish optimal anti-inflammatory drug regimens for patients with RA. Indomethacin (a 3-indolyl-acetic acid derivative) is a commonly used anti-inflammatory drug. Recent observations have been reported by Duggan, Hogans, Kwan, and McMahon (1972), on its metabolism; Hvidberg, Lausen, and Jansen (1972), on plasma concentrations and protein binding; and by Caruso (1971) on serum and synovial fluid concentrations of the drug after intravenous infusion in patients with chronic polyarthritis. This report describes the simultaneous pharmacokinetics ofindomethacin in the serum and synovial fluid of patients with RA after oral administration of the drug.