Synovial fluid and plasma kinetics of repeat dose sustained action tiaprofenic acid in patients with rheumatoid arthritis

Abstract

Tiaprofenic acid is a potent non-steroidal anti-inflammatory drug which, in conventional tablet form, has been shown to be rapidly absorbed and eliminated from the plasma, while synovial fluid concentrations remain constant for at least 8 hours. Recently, a sustained action formulation of tiaprofenic acid has been developed to provide the patient with the convenience of a once daily dosage. The purpose of this study was to measure plasma and synovial fluid concentrations over a 24-hour period following repeated administration of the sustained action formulation, and thus determine the pharmacokinetic profile. Eight patients suffering from rheumatoid arthritis were included in this open study (of whom 3 were subsequently excluded from the analysis). All were hospital outpatients requiring aspiration of the knee joint. The patients received sustained action tiaprofenic acid in a dosage of 600 mg once daily for a period of 7 days. Plasma and synovial fluid samples were taken on the final treatment day at 0, 4, 8, 12, and 18 hours following administration of the last treatment dose. Areas under the concentration-time curves, maximum plasma and synovial fluid concentrations, times to maximum concentration, and apparent elimination half-lives are presented and the findings compared and discussed. The drug was found to be retained in both the plasma and synovial fluid over a 24-hour period. Synovial fluid concentrations exceeded plasma concentrations at 24 hours in 4 of the 5 patients who were analysed, while in the fifth patient the levels were very similar.