TENOXICAM - ACUTE DOSE-DEPENDENT DISPOSITION STUDIES IN RATS

Single intravenous bolus doses of tenoxicam of 2.5, 5, and 1 0 mg/kg were administered to male Wistar rats to determine the effects of dose on tenoxidcam pharmacokinetics. Predicted apparent volume of distribution at steady state (Vd(ss)) and total plasma clearance (CL) were, respectively, 42 and 45% higher in the animals given 1 0-mg/kg dose than the animals given 2.5- and 5-mg/kg doses. Binding of tenoxicam to plasma proteins showed saturability, with a 33% higher unbound fraction of tenoxicam in plasma when total drug concentration in plasma was 36 mg/L (high dose group) in comparison with animals given the low doses (1 2 and 20 mg/L). The blood-to-plasma concentration ratio of tenoxicam was concentration independent and therefore did not account for the observed dose-dependent changes in Vd(ss) and CL.