Piroxicam concentrations in plasma and synovial fluid after a single dose of piroxicam-beta-cyclodextrin single

Aims: The efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in rheu matic diseases depends on their concentrations within the joint. We determi ned piroxicam concentrations in plasma and synovial fluid (SF) after a sing le oral dose of 20 mg in the form of one tablet of piroxicam-beta -cyclodex trin. Methods: 45 patients, aged 21 to 84 years, presenting with an effusio n of the knee, related to degenerative or inflammatory joint disease, were included in this study after having given their written consent. One blood and one SF sample were drawn concomitantly in each patient from 0.5 to 48 h after NSAID administration. Piroxicam assays were performed by high perfor mance liquid chromatography. Pharmacokinetic parameters were obtained from the mean plasma and synovial concentrations measured at various sampling ti mes. Results: The peak concentration was higher in plasma (2.51 +/- 0.25 mu g/ml) than in SF (1.31 +/- 0.76 mug/ml), but the elimination half-life was much longer in SF (90.7 h) than in plasma (32.5 h). The SF/plasma area unde r the concentration-time curve ratio (evaluating the quantity of NSAID tran sferred from the blood to the joint) was equal to 0.39. Conclusions: Piroxi cam contained in piroxicam-beta -cyclodextrin diffused well into the SF whe re its pharmacokinetic profile corresponded to that of a long half-life NSA ID.