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Clinical Pharmacokinetics

, Volume 17, Issue 3, pp 145–162 | Cite as

Recent Findings on the Pharmacokinetics of Non-Steroidal Anti-Inflammatory Drugs in Synovial Fluid

  • Patrick Netter
  • Bernard Bannwarth
  • Marie-José Royer-Morrot
Review Article Drug Disposition

Summary

Synovial fluid concentration is considered to be an important determinant of clinical response to non-steroidal anti-inflammatory drugs (NSAIDs). Trans-synovial transport of these drugs is a process of limited diffusion, governed partly by the pharmacological characteristics of NSAIDs and partly by the properties of the joint and joint space themselves.

The studies which report simultaneous pharmacokinetics of NSAIDs in both plasma and synovial fluid compartments are of 2 types: (1) some compare the concurrent concentrations of drugs in plasma and joint fluid after a single administration. These provide pharmacokinetic information; (2) others, which conform more closely to the therapeutic conditions, look at synovial fluid and plasma concentrations after repeated administration of the drug.

Recent findings on the pharmacokinetics of NSAIDs in synovial fluid are reviewed. These studies reveal 2 types of NSAIDs, according to their pharmacokinetic behaviour. First, there are NSAIDs with a short or intermediate plasma elimination half life. These drugs equilibrate rapidly relative to their elimination; their peak synovial fluid concentrations occur later and are lower than those in plasma. Several hours after administration there is crossover of the concentration curves, and beyond this point, concentrations in synovial fluid may exceed those in plasma. During prolonged treatment, the synovial fluid concentrations of these NSAIDs fluctuate to a much lesser extent than plasma concentrations. Secondly, there are NSAIDs with a long plasma elimination half life; their peak concentration in synovial fluid is also lower and later than that in plasma. At steady-state their concentrations (total and free) in synovial fluid are about half those in plasma.

Numerous variables must be taken into account in attempts to correlate synovial fluid NSAIDs concentrations with clinical response, including protein binding and determination of both active metabolites and (eventually) the enantiomers.

Keywords

Synovial Fluid Piroxicam Etodolac Tenoxicam Tiaprofenic Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© ADIS Press Limited 1989

Authors and Affiliations

  • Patrick Netter
    • 1
  • Bernard Bannwarth
    • 1
  • Marie-José Royer-Morrot
    • 1
  1. 1.Départements de Rhumatologie et de Pharmacologie CliniqueCHU de Nancy-BraboisVandoeuvre-Lès-NancyFrance

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