Physiological pharmacokinetic model for pentazocine. I. Tissue distribution and elimination in the rat

Abstract A physiologically based pharmacokinetic model was developed to describe the tissue distribution and elimination of pentazocine in the anesthetized rat. The model incorporates renal and hepatic (metabolic and biliary) elimination, GI secretion, GI reabsorption and tissue-to-blood partition coefficients. The dependency of hepatic blood flow rate on the arterial blood concentration of pentazocine is also included in the model. Excellent agreement was obtained between the predicted and observed concentrations of pentazocine in tissues and in arterial blood after a 2 mg/kg intravenous dose. Non-linear dose-dependent blood concentration-time profiles after intravenous injection of 0.5–10.0 mg/kg were successfully interpreted with the present model.