Synovial fluid drug concentrations are considered an important determinant of clinical response to NSAIDs used for joint pain and are likely to reflect blood/plasma concentrations because the synovial capsule is highly vascularized. To conform better with therapeutic conditions a study was conducted that evaluated synovial fluid and plasma drug concentrations after repeated drug administration rather than after a single dose. Results indicated that drug concentrations in synovial fluid increase with increasing plasma drug concentrations. For both drugs, average synovial fluid drug concentrations (Css,min) were >50% of the plasma drug concentrations (Css,min) at steady state. After 8 days of treatment, the average firocoxib plasma Css,min was 70.7 � 22.9 ng/mL and the corresponding synovial fluid Css,min was 44.1 � 20.0 ng/mL. The average phenylbutazone plasma Css,min was 772 � 434 ng/mL and the synovial fluid Css,min was 380 � 151 ng/mL. The depletion of drug from synovial fluid and plasma followed a similar exponential decay.

Pharmacokinetics and synovial fluid/plasma drug ratios of firocoxib and phenylbutazone in horses after repeated drug administration

246th National Meeting (2013)

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