Antirheumatic Drug Concentrations in Human Synovial Fluid and Synovial Tissue

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.

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

“…Most studies on the pharmacokinetics of drugs in synovial fluid have been based on single or serial sampling of the knee effusion after oral administration of drug [1,5]. The present work sought to assess drug efflux from the joint after intra-articular injection.…”

“…Wallis & Simkin [5] after intra-articular injection and include sodium [6,7], iodine [8] and xenon [9]. Simkin & Pizzorno [10] injected a number of solutes together into healthy knees and reported that the synovial fluid to blood flux of small molecules is limited mainly by diffusion.…”

Diclofenac concentrations in synovial fluid and plasma after cutaneous application in inflammatory and degenerative joint disease.

“…The differences in plasma and synovial fluid total drug concentrations could be due to differences in protein content (Wallis & Simkin, 1983) or protein composition (Wallis & Simkin, 1983 (Wagner & Sulc, 1979). The extent of drug binding in synovial fluid was significantly less than in plasma (0.29 ± 0.04 vs 0.52 ± 0.07%, P < 0.05), confirming the finding of Chan et al (1987).…”

The value of synovial fluid assays in the diagnosis of joint disease: a literature survey

“…41 However, it is difficult to interpret the meaning of a single measurement of the concentration of any of these molecules in SF, because of our lack of understanding of the dynamics of their movement through the joint space.…”