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Nonsteroidal anti-inflammatory drugs are an important part of the therapy of rheumatoid arthritis. For optimal dosage it would be necessary to know the levels of such compounds in inflamed tissue and not only in blood because the drugs inhibit prostaglandin synthesis in all cells of the body. In the present study, the levels of indomethacin in blood, synovial fluid, synovial membrane, muscle, fat, bone and spinal fluid of patients with rheumatoid arthritis have been measured at 1, 3, 6, and 12 hours after administration of 50 mg indomethacin (Amuno, Merck Sharp & Dohme). At 3, 6, 9 and 12 hours after administration levels in synovial fluid and tissue were higher than in blood but the differences were not significant. Levels in the other tissues investigated did not differ much from blood. In experiments with carrageenan-induced inflammation in rabbits, levels of indomethacin in blood and exudate have been measured after administration of 7.5 mg/kg i.v. Between 3 and 8 hours after administration levels in exudate were significantly higher than in blood. From the time course of indomethacin in blood compared to synovial fluid or exudate and from the comparison of the elimination half lives it can be concluded, that the transport of indomethacin into the inflamed area is mainly a process of diffusion.
P Dittrich, and
G Köhler, and
P Primbs, and
W R Kukovetz
September 1973,
Annals of the rheumatic diseases,
P Dittrich, and
G Köhler, and
P Primbs, and
W R Kukovetz
November 1971,
Arzneimittel-Forschung,
P Dittrich, and
G Köhler, and
P Primbs, and
W R Kukovetz
January 1976,
Rheumatology and rehabilitation,
P Dittrich, and
G Köhler, and
P Primbs, and
W R Kukovetz
December 1946,
Lancet (London, England),
P Dittrich, and
G Köhler, and
P Primbs, and
W R Kukovetz
October 2017,
Antimicrobial agents and chemotherapy,
P Dittrich, and
G Köhler, and
P Primbs, and
W R Kukovetz
February 1972,
La Nouvelle presse medicale,
P Dittrich, and
G Köhler, and
P Primbs, and
W R Kukovetz
January 2004,
Clinical pharmacokinetics,
P Dittrich, and
G Köhler, and
P Primbs, and
W R Kukovetz
October 1979,
Journal of clinical pharmacology,
P Dittrich, and
G Köhler, and
P Primbs, and
W R Kukovetz
June 1990,
British journal of anaesthesia,
P Dittrich, and
G Köhler, and
P Primbs, and
W R Kukovetz
December 1983,
La semaine des hopitaux : organe fonde par l'Association d'enseignement medical des hopitaux de Paris,
