The pharmacokinetics of total and unbound concentrations of tenoxicam in synovial fluid and plasma

Abstract

Tenoxicam is a nonsteroidal antiinflammatory drug with an elimination half-life of 60-80 hours; it is administered once daily. Tenoxicam concentrations were measured in plasma (10 samples) and synovial fluid (6 samples) over a 24-hour dosage interval at steady state in 10 subjects with arthritis who had been taking the drug at a dosage of 20 mg/day for at least 2 weeks. Total tenoxicam concentrations in synovial fluid were always less than those in plasma, and there was little fluctuation in plasma or synovial concentrations over the dosage interval, although there was substantial inter-subject variation in both concentrations. There was a significant relationship between the tenoxicam dosage when expressed as mg/kg of body weight and the average steady-state total concentration of tenoxicam in plasma (r = 0.80, P = 0.006); this accounted for a substantial proportion of the intersubject variation. The mean +/- SD steady-state concentrations in synovial fluid and plasma were 3.9 +/- 1.8 micrograms/ml and 9.2 +/- 3.7 micrograms/ml, respectively, yielding a mean +/- SD synovial fluid: plasma ratio of 0.43 +/- 0.12. Synovial fluid:plasma ratios of total tenoxicam correlated with synovial fluid:plasma ratios of albumin (r = 0.71, P = 0.02). The synovial fluid:plasma ratio of unbound tenoxicam was 0.90 +/- 0.3 (95% confidence interval 0.68-1.11), which was not significantly different from a value of 1 (t = -1.09, P = 0.31).