• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of brjclinpharmLink to Publisher's site
Br J Clin Pharmacol. Oct 1994; 38(4): 349–355.
PMCID: PMC1364779

Disappearance kinetics of solutes from synovial fluid after intra-articular injection.

Abstract

1. Five rheumatoid patients with a knee joint effusion participated in the study. An aqueous solution (0.1 to 0.2 ml) containing paracetamol, salicylate, diclofenac and [125I]-albumin was injected into a given joint to yield target concentrations of approximately 20 micrograms ml-1 for diclofenac, salicylate and paracetamol and 10(8) counts ml-1 for [125I]-albumin. 2. Paracetamol, salicylate and diclofenac were analysed in synovial fluid by h.p.l.c. [125I]-albumin was analysed using gamma counting. 3. The clearances (+/- s.d.) obtained for the solutes were [125I]-albumin (0.0053 +/- 0.0019 l h-1), diclofenac (0.0096 +/- 0.0061 l h-1), salicylate (0.024 +/- 0.022 l h-1) and paracetamol (0.055 +/- 0.041 l h-1). The corresponding fractions unbound of these solutes in synovial fluid were 0.0, < or = 0.01, 0.34 +/- 0.09 and 0.85 +/- 0.10, respectively. 4. Diffusion of unbound solute through the synovium is estimated to account for (+/- s.d.) 0.52 +/- 0.08, 0.87 +/- 0.06 and 0.99 +/- 0.01 of the total clearance of diclofenac, salicylate and paracetamol from the joint space, respectively. The remaining proportion of clearance is accounted for by efflux of solute bound to albumin. 5. An expression for the ratio of synovial fluid to total plasma concentrations after systemic administration was developed to include both diffusion of unbound solute and albumin flux. Most solutes appear to satisfy the conditions in which this expression reduces to the limiting case where the unbound concentration of the solute is identical in the synovial fluid and plasma under steady state conditions.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.2M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Netter P, Bannwarth B, Royer-Morrot MJ. Recent findings on the pharmacokinetics of non-steroidal anti-inflammatory drugs in synovial fluid. Clin Pharmacokinet. 1989 Sep;17(3):145–162. [PubMed]
  • Verbeeck RK, Blackburn JL, Loewen GR. Clinical pharmacokinetics of non-steroidal anti-inflammatory drugs. Clin Pharmacokinet. 1983 Jul-Aug;8(4):297–331. [PubMed]
  • Lin JH, Cocchetto DM, Duggan DE. Protein binding as a primary determinant of the clinical pharmacokinetic properties of non-steroidal anti-inflammatory drugs. Clin Pharmacokinet. 1987 Jun;12(6):402–432. [PubMed]
  • Furst DE. Synovial fluid kinetics of non-steroidal anti-inflammatory drugs. Agents Actions Suppl. 1985;17:65–78. [PubMed]
  • Wallis WJ, Simkin PA. Antirheumatic drug concentrations in human synovial fluid and synovial tissue. Observations on extravascular pharmacokinetics. Clin Pharmacokinet. 1983 Nov-Dec;8(6):496–522. [PubMed]
  • JACOX RF, JOHNSON MK, KOONTZ R. Transport of radioactive sodium across the synovial membrane of normal human subjects. Proc Soc Exp Biol Med. 1952 Aug-Sep;80(4):655–657. [PubMed]
  • HARRIS R, MILLARD JB, BANERJEE SK. Radiosodium clearance from the knee joint in rheumatoid arthritis. Ann Rheum Dis. 1958 Jun;17(2):189–195. [PMC free article] [PubMed]
  • St Onge RA, Dick WC, Bell G, Boyle JA. Radioactive xenon (133Xe) disappearance rates from the synovial cavity of the human knee joint in normal and arthritic subjects. Ann Rheum Dis. 1968 Mar;27(2):163–166. [PMC free article] [PubMed]
  • Simkin PA, Pizzorno JE. Transynovial exchange of small molecules in normal human subjects. J Appl Physiol. 1974 May;36(5):581–587. [PubMed]
  • Owen SG, Roberts MS, Friesen WT. Rapid high-performance liquid chromatographic assay for the simultaneous analysis of non-steroidal anti-inflammatory drugs in plasma. J Chromatogr. 1987 May 15;416(2):293–302. [PubMed]
  • Rumble RH, Roberts MS, Wanwimolruk S. Determination of aspirin and its major metabolites in plasma by high-performance liquid chromatography without solvent extraction. J Chromatogr. 1981 Sep 11;225(1):252–260. [PubMed]
  • Chan KK, Vyas KH, Brandt KD. In vitro protein binding of diclofenac sodium in plasma and synovial fluid. J Pharm Sci. 1987 Feb;76(2):105–108. [PubMed]
  • Wallis WJ, Simkin PA, Nelp WB, Foster DM. Intraarticular volume and clearance in human synovial effusions. Arthritis Rheum. 1985 Apr;28(4):441–449. [PubMed]
  • Wigginton SM, Chu BC, Weisman MH, Howell SB. Methotrexate pharmacokinetics after intraarticular injection in patients with rheumatoid arthritis. Arthritis Rheum. 1980 Jan;23(1):119–122. [PubMed]
  • Day RO, Williams KM, Graham GG, Lee EJ, Knihinicki RD, Champion GD. Stereoselective disposition of ibuprofen enantiomers in synovial fluid. Clin Pharmacol Ther. 1988 May;43(5):480–487. [PubMed]
  • ROSENTHAL RK, BAYLES TB, FREMONT-SMITH K. SIMULTANEOUS SALICYLATE CONCENTRATIONS IN SYNOVIAL FLUID AND PLASMA IN RHEUMATOID ARTHRITIS. Arthritis Rheum. 1964 Apr;7:103–109. [PubMed]
  • Aarons L, Salisbury R, Alam-Siddiqi M, Taylor L, Grennan DM. Plasma and synovial fluid kinetics of flurbiprofen in rheumatoid arthritis. Br J Clin Pharmacol. 1986 Feb;21(2):155–163. [PMC free article] [PubMed]
  • Netter P, Bannwarth B, Lapicque F, Harrewyn JM, Frydman A, Tamisier JN, Gaucher A, Royer RJ. Total and free ketoprofen in serum and synovial fluid after intramuscular injection. Clin Pharmacol Ther. 1987 Nov;42(5):555–561. [PubMed]
  • Kraml M, Hicks DR, McKean M, Panagides J, Furst D, Furst J. The pharmacokinetics of etodolac in serum and synovial fluid of patients with arthritis. Clin Pharmacol Ther. 1988 May;43(5):571–576. [PubMed]
  • Simkin PA, Wu MP, Foster DM. Articular pharmacokinetics of protein-bound antirheumatic agents. Clin Pharmacokinet. 1993 Oct;25(4):342–350. [PubMed]
  • Jayson MI, St Dixon AJ. Intra-articular pressure in rheumatoid arthritis of the knee. I. Pressure changes during passive joint distension. Ann Rheum Dis. 1970 May;29(3):261–265. [PMC free article] [PubMed]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem Compound links
  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...