Protein binding of non-steroidal anti-inflammatory drugs in plasma and synovial fluid of arthritic patients.

1 The protein binding of seven non-steroidal anti-inflammatory drugs (indomethacin, tolmetin, salicylic acid, ibuprofen, flurbiprofen, naproxen and GP53,633) and warfarin was investigated by equilibrium dialysis in simultaneous samples of synovial fluid and plasma from 12 arthritic patients. 2 The protein binding of all drugs studied except warfarin and flurbiprofen was significantly lower in synovial fluid than in plasma. 3 The decreased protein binding of these drugs is likely to explain the lower total drug concentrations found in synovial fluid in comparison to plasma. 4 The lower albumin concentration plays an important role in determination of reduced drug binding in synovial fluid compared to plasma and the fatty acid concentration in synovial fluid may also influence the protein binding of some of these drugs.