Physiological pharmacokinetic model for the distribution and elimination of tenoxicam

A physiologically based pharmacokinetic model for tenoxicam distribution and excretion in the rat was developed. The drug concentrations in plasma and all the tissues except testis were simulated using flow-limited equations, while testis concentrations were calculated using a membrane-limited passive diffusion equation. The elimination of tenoxicam was described in the model by renal and hepatic (metabolic and biliary) excretion with gastro-intestinal secretion and reabsorption. In order to validate the model, 15 tissue samples, plasma (for free and total concentration), urine and feces samples were collected and assayed by HPLC after i.v. injection of tenoxicam (4.5 mg/kg). Good agreements between simulation and experimental data over a 24-h period following drug administration were obtained for plasma and tissues. The terminal half-life of tenoxicam was 8.8 h in plasma and ranged in tissues from 6.1 h in intestine to 10.6 h in brain. The fraction of free tenoxicam in plasma ranged from 1.2 to 2.1% of the total tenoxicam concentration (5.7-21.9 μ/ml).