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PMID: 6360465 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Review

Antirheumatic drug concentrations in human synovial fluid and synovial tissue. Observations on extravascular pharmacokinetics.

Clinical pharmacokinetics ·Vol. 8 ·No. 6 ·1983-00-00 ·Pages 496-522

Wallis WJ, Simkin PA

Abstract

Antirheumatic drug concentrations have been measured in human synovial fluid and synovial tissue, and provide insights on: (1) extravascular pharmacokinetics; (2) articular pathophysiology; and (3) the factors which modify drug levels in inflamed tissues. Concentrations of free drug in synovial fluid and plasma are the same in all conditions except rheumatoid and infectious arthritis, where the most severely afflicted joints may contain lower synovial fluid drug concentrations. This finding may be relevant to the chronicity and intractability of chronic arthritis. After single-dose therapy and a characteristic 'equilibration time', higher concentrations are found in synovial fluid than in plasma - a phenomenon which results from relative drug sequestration across the trans-synovial diffusion barrier away from the organs of elimination. Studies of oral, parenteral, topical and intra-articular antirheumatic drug therapy are reviewed, and recommendations are made for the conduct of future studies.

MeSH Terms
Anti-Inflammatory Agents/metabolism Half-Life Humans Injections Kinetics Protein Binding Solubility Synovial Fluid/metabolism Synovial Membrane/metabolism
Chemicals
Anti-Inflammatory Agents
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Wallis W J
Simkin P A
References (71)
71 references, click to expand
  1. THE MANNER OF REMOVAL OF PROTEINS FROM NORMAL JOINTS.
    J Exp Med. 1933 Feb 28;57(3):419-33 PMID: 19870140
  2. Clinical pharmacokinetics of salicylates: a re-assessment.
    Br J Clin Pharmacol. 1980 Oct;10 Suppl 2:285S-290S PMID: 7437270
  3. Disposition and metabolism of intra-articularly injected 4-C14-cortisol in rheumatoid arthritis.
    Arthritis Rheum. 1967 Aug;10(4):352-6 PMID: 6046017
  4. Dissociation of acetylsalicylic acid in blood and joint fluid.
    Scand J Rheumatol. 1977;6(1):17-22 PMID: 850778
  5. Long-duration intracavitary infusion of methotrexate with systemic leucovorin protection in patients with malignant effusions.
    J Clin Invest. 1981 Apr;67(4):1161-70 PMID: 6970753
  6. METABOLISM, TOXICITY AND MANNER OF ACTION OF GOLD COMPOUNDS USED IN THE TREATMENT OF ARTHRITIS. I. HUMAN PLASMA AND SYNOVIAL FLUID CONCENTRATION AND URINARY EXCRETION OF GOLD DURING AND FOLLOWING TREATMENT WITH GOLD SODIUM THIOMALATE, GOLD SODIUM THIOSULFATE, AND COLLOIDAL GOLD SULFIDE.
    J Clin Invest. 1941 Jul;20(4):401-12 PMID: 16694848
  7. The distribution of antibacterial agents between plasma and lymph in the dog.
    Br J Pharmacol. 1970 Jun;39(2):439-46 PMID: 4987520
  8. Respiratory gases of synovial fluids. An approach to synovial tissue circulatory-metabolic imbalance in rheumatoid arthritis.
    Am J Med. 1970 Aug;49(2):223-31 PMID: 5452943
  9. Comparison of intra-articular methotrexate with intra-articular triamcinolone hexacetonide by thermography.
    Curr Med Res Opin. 1977;5(2):141-6 PMID: 340129
  10. Protein binding of tolmetin.
    Clin Pharmacol Ther. 1978 Dec;24(6):694-705 PMID: 710027
  11. Studies with radioactive gold.
    Ann Rheum Dis. 1961 Dec;20:341-52 PMID: 14462996
  12. Yttrium 90 in persistent synovitis of the knee - a single centre comparison. The retention and extra-articular spread of four 90-U radiocolloids.
    Br J Radiol. 1975 May;48(569):377-81 PMID: 1139094
  13. Lipid solubility and drug penetration of the blood brain barrier.
    Proc Soc Exp Biol Med. 1974 Dec;147(3):813-5 PMID: 4445171
  14. Free versus bound salicylate concentration in adults and children with chronic inflammatory joint disease: serum albumin and other potential factors affecting the levels.
    Arthritis Rheum. 1982 Jan;25(1):32-7 PMID: 7066035
  15. Studies on the metabolism of adrenal cortical steroids in the synovial cavity in rheumatoid arthritis.
    Ann N Y Acad Sci. 1955 May 27;61(2):502-10 PMID: 13249270
  16. Albumin metabolism in rheumatoid arthritis.
    Ann Rheum Dis. 1971 May;30(3):265-70 PMID: 5090242
  17. The passage of benorylate into the synovial fluid and tissue of rheumatoid patients.
    Scand J Rheumatol Suppl. 1975;13:18-20 PMID: 8834
  18. Methotrexate pharmacokinetics after intraarticular injection in patients with rheumatoid arthritis.
    Arthritis Rheum. 1980 Jan;23(1):119-22 PMID: 6965451
  19. Rate of disappearance and metabolism of hydrocortisone and cortisone in the synovial cavity in rheumatoid arthritis.
    Proc Soc Exp Biol Med. 1953 Jul;83(3):648-54 PMID: 13088938
  20. Transynovial exchange of small molecules in normal human subjects.
    J Appl Physiol. 1974 May;36(5):581-7 PMID: 4826322
  21. A physiological approach to the assessment of disease activity in rheumatoid arthritis.
    J Clin Invest. 1971 Jun;50(6):1167-80 PMID: 5578228
  22. Synovial permeability in rheumatoid arthritis.
    Arthritis Rheum. 1979 Jul;22(7):689-96 PMID: 454497
  23. Penetration of antibiotics into fibrin loci in vivo. II. Comparison of nine antibiotics: effect of dose and degree of protein binding.
    J Infect Dis. 1974 Jan;129(1):66-72 PMID: 4809114
  24. [Time of persistence of fluocortolone hexanoate in the knee-joint after intra-articular injection (author's transl)].
    Dtsch Med Wochenschr. 1979 Feb 23;104(8):293-5 PMID: 761531
  25. Permeability of human synovial membrane to plasma proteins. Relationship to molecular size and inflammation.
    Arthritis Rheum. 1971 Sep-Oct;14(5):560-70 PMID: 4106176
  26. Concentration of antibacterial agents in interstitial tissue fluid.
    Br Med J. 1973 Mar 10;1(5853):569-73 PMID: 4694402
  27. Intra-articular methotrexate. Clinical and laboratory study in rheumatoid and psoriatic arthritis.
    Ann Rheum Dis. 1978 Aug;37(4):351-6 PMID: 356763
  28. Characterization of salicylate binding to synovial fluid and plasma protein in patients with rheumatoid arthritis.
    Eur J Clin Pharmacol. 1980 Nov;18(5):403-6 PMID: 7439262
  29. Concentrations of flurbiprofen in serum and synovial fluid from patients with active rheumatoid disease: some preliminary observations.
    Curr Med Res Opin. 1977;5(1):17-20 PMID: 303167
  30. Use of yttrium 90 in persistent synovitis of the knee. I. Retention in the knee and spread in the body after injection.
    Ann Rheum Dis. 1973 May;32(3):223-7 PMID: 4715540
  31. Pharmacodynamics of 197Au and 195Au labeled aurothiomalate in blood. Correlation with course of rheumatoid arthritis, gold toxicity and gold excretion.
    Arthritis Rheum. 1974 Mar-Apr;17(2):171-83 PMID: 4814979
  32. Relationship of plasma digitoxin and digoxin to cardiac response following intravenous digitalization in man.
    Circulation. 1970 Dec;42(6):1065-72 PMID: 5492538
  33. Pharmacokinetics of carprofen in plasma and synovial fluid.
    J Clin Pharmacol. 1979 Oct;19(10):635-43 PMID: 512061
  34. Pharmacokinetic analysis of the effect of theophylline on pulmonary function in asthmatic children.
    J Pediatr. 1975 May;86(5):789-93 PMID: 1133663
  35. Transport of salicylates from blood to joint fluid.
    Arch Intern Med. 1973 Nov;132(5):668-72 PMID: 4750223
  36. Plasma and synovial fluid pharmacokinetics and prostaglandin inhibitory effect of indoprofen in patients with rheumatoid arthritis.
    Scand J Rheumatol. 1980;9(2):123-6 PMID: 7433927
  37. Retention of 90Y in patients with rheumatoid arthritis.
    Ann Rheum Dis. 1973 Dec;32 Suppl 6:Suppl:38-40 PMID: 4358683
  38. Absorption and excretion of tolmetin in arthritic patients.
    Clin Pharmacol Ther. 1979 Jul;26(1):122-8 PMID: 445955
  39. Simultaneous pharmacokinetics of benorylate in plasma and synovial fluid of patients with rheumatoid arthritis.
    Scand J Rheumatol Suppl. 1975;13:9-12 PMID: 8841
  40. Comparative tissue absorption of oral 14C-aspirin and topical triethanolamine 14C-salicylate in human and canine knee joints.
    J Clin Pharmacol. 1982 Jan;22(1):42-8 PMID: 6977559
  41. Anion transport from the canine synovial cavity.
    Nat New Biol. 1971 May 12;231(19):61-3 PMID: 4326680
  42. Absorption and excretion of tolemetin in man.
    Clin Pharmacol Ther. 1976 Feb;19(2):224-33 PMID: 1261159
  43. Synovial fine structure and permeability after intra-articular nitrogen mustard.
    Arch Pathol. 1968 Feb;85(2):162-74 PMID: 5635192
  44. Role of pharmacokinetics in drug dosage adjustment. I. Pharmacologic effect kinetics and apparent volume of distribution of digoxin.
    J Clin Pharmacol New Drugs. 1973 Apr;13(4):127-41 PMID: 4487163
  45. Total and free-plasma tryptophan concentrations in rheumatoid disease.
    J Pharm Pharmacol. 1973 Jul;25(7):570-2 PMID: 4147056
  46. Simultaneous pharmacokinetics of indomethacin in serum and synovial fluid.
    Ann Rheum Dis. 1973 Sep;32(5):433-5 PMID: 4751781
  47. Transsynovial distribution of ibuprofen in arthritic patients.
    Clin Pharmacol Ther. 1981 Apr;29(4):487-92 PMID: 7471614
  48. The aurosome.
    J Rheumatol Suppl. 1979;5:45-50 PMID: 114648
  49. SIMULTANEOUS SALICYLATE CONCENTRATIONS IN SYNOVIAL FLUID AND PLASMA IN RHEUMATOID ARTHRITIS.
    Arthritis Rheum. 1964 Apr;7:103-9 PMID: 14150739
  50. Tissue gold concentration in a rheumatoid arthritic receiving chrysotherapy.
    Arthritis Rheum. 1972 Jan-Feb;15(1):16-22 PMID: 5059639
  51. Localization of gold in synovial membrane of rheumatoid arthritis treated with sodium aurothiomalate. Studies by electron microscope and electron probe x-ray microanalysis.
    Ann Rheum Dis. 1977 Jun;36(3):209-15 PMID: 406861
  52. Investigation of phenylbutazone in synovial fluid.
    J Int Med Res. 1977;5 Suppl 2:26-9 PMID: 913871
  53. DA 2370 serum and synovial fluids concentrations in patients with rheumatoid arthritis.
    Curr Med Res Opin. 1974;2(1):51-6 PMID: 4842318
  54. Kinetics of aurothiomalate in serum and synovial fluid.
    Arthritis Rheum. 1972 Nov-Dec;15(6):625-9 PMID: 4628732
  55. [Distribution of indomethacin in blood and synovial fluid of patients with rheumatoid arthritis].
    Arzneimittelforschung. 1971 Nov;21(11):1824-6 PMID: 5171813
  56. Absorption from the synovial cavity in rabbits and cats. The influence of different environments and drugs.
    S Afr J Med Sci. 1967 Oct;32(3):83-95 PMID: 5582548
  57. Protein binding of some non-steroidal anti-inflammatory drugs in rheumatoid arthritis.
    Clin Pharmacokinet. 1982 Jan-Feb;7(1):85-92 PMID: 7075085
  58. The distribution of proquazone and three of its metabolites in serum and synovial fluid.
    Scand J Rheumatol Suppl. 1978;(21):12-4 PMID: 278176
  59. Disposition of intraarticularly injected cortisone and hydrocortisone.
    Arthritis Rheum. 1959 Oct;2:433-9 PMID: 14432256
  60. Transport time for salicylates from blood to joint fluid-- a test of histopathology of the synovial membrane.
    Z Rheumatol. 1975 May-Jun;34(5-6):213-20 PMID: 1229742
  61. Experimental osteoarthritis in the rabbit. A study of 133xenon washout rates from the synovial cavity.
    Acta Orthop Scand. 1982 Apr;53(2):167-74 PMID: 7136561
  62. Naproxen concentrations in serum, synovial fluid, and synovium.
    Scand J Rheumatol. 1977;6(3):155-7 PMID: 929122
  63. Plasma and synovial fluid concentrations of acetylsalicylic acid in patients with rheumatoid arthritis.
    Arthritis Rheum. 1967 Aug;10(4):348-51 PMID: 6046016
  64. Absorption of hydrocortisone from the joint cavity into the circulation.
    Ann Rheum Dis. 1956 Dec;15(4):327-9 PMID: 13395265
  65. Amino acid composition of serum albumin in normal individuals and in patients with rheumatoid arthritis.
    Clin Chem. 1970 Jan;16(1):54-7 PMID: 5414122
  66. Aspirin survival in human blood modulated by the concentration of erythrocytes.
    Arthritis Rheum. 1982 May;25(5):550-5 PMID: 7082400
  67. Simultaneous pharmacokinetics of alclofenace in plasma and synovial fluid in patients with rheumatoid arthritis.
    Curr Med Res Opin. 1975;3(5):264-7 PMID: 241595
  68. Salicylates in blood and joint fluid after ingestion of buffered aspirin.
    Clin Orthop Relat Res. 1970 Jan-Feb;68:322-8 PMID: 5414720
  69. Significance of xenon-133 clearance rate from canine and human joints.
    Arthritis Rheum. 1972 Jul-Aug;15(4):360-70 PMID: 5046467
  70. Distribution of benorylate in plasma, synovial fluid and tissue in rheumatoid arthritis.
    Scand J Rheumatol Suppl. 1975;13:13-7 PMID: 8833
  71. Ibuprofen levels in serum and synovial fluid.
    Scand J Rheumatol Suppl. 1981;39:15-7 PMID: 6946551
Article Info
Journal
Clinical pharmacokinetics
Abbr.
Clin Pharmacokinet
ISSN
0312-5963
DOI
10.2165/00003088-198308060-00002
Published
1983-00-00
Pages
496-522
Language
English
Region
Switzerland
NLM ID
7606849
Subset
IM
Grants
NIADDK NIH HHS · AM 22186 · United States
NIADDK NIH HHS · T32 AM 07108 · United States
External Links
PubMed source DOI: 10.2165/00003088-198308060-00002 View journal details
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