PMID: 3262939Jan 1, 1988Paper

Integrated plasma and synovial fluid pharmacokinetics of tenoxicam in patients with rheumatoid arthritis and osteoarthritis: factors determining the synovial fluid/plasma distribution ratio

Therapeutic Drug Monitoring
P H HinderlingP Heizmann

Abstract

Single oral doses of 40 mg of the nonsteroidal antiinflammatory drug, tenoxicam, were given to four patients (three with rheumatoid arthritis, one with osteoarthritis). The concentrations of the drug in synovial fluid and plasma were measured by a specific high-performance liquid chromatography method. The unbound fractions of the drug in both fluids were determined at pH 7.4 and 37 degrees C by equilibrium dialysis. The possible influence of the pH on the protein binding was also assessed. The total concentration time curves in plasma and synovial fluid were fitted to linear oral 1 and 2 compartment body models with an additional synovial fluid compartment connected to the central compartment. The unbound fractions of drug in synovial fluid and plasma were on average 0.015 and 0.011, respectively: not significantly different from each other. The protein binding of tenoxicam was pH dependent with increased free fractions at pH values less than 7.4. The average peak concentrations of tenoxicam in plasma and synovial fluid were 4.3 and 1.4 micrograms/ml, respectively. The mean ratio of the areas under the total concentration time curves in synovial fluid and plasma was 0.42, which corresponded to the steady state of equilibrium r...Continue Reading

Citations

Mar 1, 1991·Agents and Actions·B BannwarthA Gaucher
Jan 25, 2005·Therapeutic Drug Monitoring·Peter H Hinderling, Dieter Hartmann

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