Summary
The diffusion of oxyphenbutazone into synovial and cerebrospinal fluids and synovium and joint cartilage was investigated in 25 patients receiving short-term treatment. In the synovial fluid, the mean oxyphenbutazone concentration, was 57.1±13.4% of the plasma level, due to its excellent diffusion into the joint cavity. In synovial tissue, the oxyphenbutazone level was higher in patients with severe inflammation than in those with no or little inflammation. Penetration into joint cartilage is less than into synovial tissue. In cerebrospinal fluid the concentration was close to the level of free plasma oxyphenbutazone. The findings show increased diffusion of oxyphenbutazone towards its site of action in inflammation.
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Aylward M, Maddock J, Rees P, Thomas GM, Wheeldon R, Holly F (1976) Simultaneous pharmacokinetics of benorylate in plasma and synovial fluid of patients with rheumatoid arthritis. Scand J Rheumatol 13 [Suppl]: 9–12
Caruso I (1971) Verteilung von Indometacin in Blut und Synovialflüssigkeit chronischer Polyarthritiker. Arzneim Forsch 21: 1824–6
Caruso I, Moro E, Patrono C, Sacchetti G, Tamassia V, Tosolini GP (1980) Plasma and synovial fluid pharmacokinetics and prostaglandin inhibitory effect of indoprofen in patients with rheumatoid arthritis. Scand J Rheumatol 9: 123–6
Chalmers TM, Glass RC, Risdall PC (1977) Concentrations of flurbiprofen in serum and synovial fluid from patients with active rheumatoid disease: Some preliminary observations. Curr Med Res Opin 5: 17–20
Chiccarelli FS, Eisner HJ, Van Lear GE (1980) Metabolic and pharmacokinetic studies with fenbufen in man. Arzneim Forsch 30: 728–35
Daymond TJ, Herbert R (1982) Simultaneous bioavailability of tiaprofenic acid (Surgam) in serum and synovial fluid in patients with rheumatoid arthritis. Rheumatology 7: 188–93
Dell HD, Fiedler T, Jacobi H, Wasche B (1977) Zur Biochemie und Pharmacokinetik von Etofenamat. Untersuchungen am Menschen. Arzneim Forsch 27: 1322–5
Emori HW, Champion GD, Bluestone R, Paulus HE (1973) Simultaneous pharmacokinetics of indomethacin in serum and synovial fluid. Ann Rheum Dis 32: 433–5
Farr M (1977) Investigation of phenylbutazone in synovial fluid. J Int Med Res 5 [Suppl]: 26–9
Farr M, Hawkins CF, Kendall MJ, Willis JV (1982) Some observations and speculations on the factors influencing the concentration of phenylbutazone in synovial fluid. Int J Clin Pharmacol Ther Toxicol 20: 589–94
Franke M, Manz G, Glynn JP (1976) Distribution of benorylate in plasma, synovial fluid and tissue in rheumatoid arthritis. Scand J Rheumatol 13 [Suppl]: 13–7
Glass RC, Swannel AJ (1978) Concentrations of ibuprofen in serum and synovial fluid from patients with arthritis. Brit J Clin Pharmacol 6: 453–454
Graf P, Glatt M, Brune K (1975) Acidic nonsteroid anti-inflammatory drugs accumulating in inflamed tissue. Experientia 31: 951–3
Hamalainen M, Laine VA, Penn RG, Vainio K (1973) The passage of benorylate into the synovial fluid and tissue of rheumatoid patients. A symposium on benorylate. Rheumatol Rehabil 12 [Suppl]: 85–91
Jalava S, Saarimaa H, Anttila M, Sundquist H (1977) Naproxen concentrations in serum synovial fluid and synovium. Scand J Rheumatol 6: 155–7
Köhler G, Dell HD, Kamp R (1981) Gewebekonzentration nicht-steroidaler Entzündungshemmer bei Patienten mit chronischer Polyarthritis. Z Rheumatol 40: 97–9
Köhler G, Mohing W (1980) Zur Kinetik von Diclofenac-Na in Plasma und Synovialflüssigkeit. Akt Rheumatol 5: 151–5
Laine VA, Penn RG, Patiala H, Sibelius R (1976) The passage of benorylate into the synovial fluid and tissue of rheumatoid patients. Scand J Rheumatol 13 [Suppl]: 18–20
Mäkelä AL, Lempiäinen M, Ylijoki H (1981) Ibuprofen levels in serum and synovial fluid. Scand J Rheumatol 39 [Suppl]: 15–7
Manz G, Glynn JP (1975) Die Verteilung von Benorilat in Plasma, Synovialflüssigkeit und Synovialgewebe bei rheumatoider Arthritis. Z Rheumatol 34: 400–7
Mitchell WS, Scott P, Kennedy AC, Brooks PM, Templeton R, Jeffries MG (1975) Clinico-pharmacological studies on ketoprofen (‘Orudis’) Curr Med Res Opin 3: 423–30
Ott H, Meier J (1978) The distribution of proquazone and three of its metabolites in serum and synovial fluid. Scand J Rheumatol 21 [Suppl]: 12–4
Ray JE, Wade DN, Graham GG, Day RO (1979) Pharmacokinetics of carprofen in plasma and synovial fluid. J Clin Pharmacol 19: 635–43
Rosenthal RK, Bayles TB, Fremont-Smith K (1964) Simultaneous salicylate concentrations in synovial fluid and plasma in rheumatoid arthritis. Arthritis Rheum 2: 103–9
Scott RW, Thoburn TW, Hanzlik PJ (1917) The salicylates. IV. Salicylate in the blood and joint fluid of individuals receiving full therapeutic doses of the drug. J Pharmacol Exp Ther 9: 217–25
Sholkoff SD, Eyring EJ, Rowland M, Riegelman S (1967) Plasma and synovial fluid concentrations of acetylsalicylic acid in patients with rheumatoid arthritis. Arthritis Rheum 10: 348–51
Simon LS, Mills JA (1980) Nonsteroidal anti-inflammatory drugs. N Engl J Med 302: 1179–85
Soren A (1970) Salicylates in blood and joint fluid after ingestion of buffered aspirin. Clin Orthop 68: 322–8
Soren A (1977) Dissociation of acetylsalicylic acid in blood and joint fluid. Scand J Rheumatol 6: 17–22
Thomas GM, Rees P, Dippy JE, Maddock J (1975) Simultaneous pharmacokinetics of alclofenac in plasma and synovial fluid in patient with rheumatoid arthritis. Curr Med Res Opin 3: 264–7
Whitlam JB, Brown KF, Crooks MJ, Romm GFW (1981) Transsynovial distribution of Ibuprofen in arthritic patients. Clin Pharmacol Ther 29: 487–92
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Gaucher, A., Netter, P., Faure, G. et al. Diffusion of oxyphenbutazone into synovial fluid, synovial tissue, joint cartilage and cerebrospinal fluid. Eur J Clin Pharmacol 25, 107–112 (1983). https://doi.org/10.1007/BF00544025
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DOI: https://doi.org/10.1007/BF00544025