Abstract
A physiologically based pharmacokinetic model was applied to describe the distribution and elimination of pentazocine in rabbits. For the elimination of pentazocine, the model consisted of renal, hepatic (metabolic and biliary), and GI secretion and Gl re-absorption. The tissue-to-blood partition coefficients of pentazocine in the rabbit were almost the same with those in the rat. No significant variation in hepatic blood flow rate dependent on the arterial blood concentration of pentazocine was observed in the rabbit, the results being very different from those in the rat. The time course of blood concentration after intravenous injection was proportional to dose in the range of 0.5–10 mg/kg. Excellent agreements were obtained between the predicted and observed concentrations of pentazocine after intravenous administration in the rabbit. Application of the rabbit model to prediction in man by considering the differences in organ volume, organ blood flow and renal pentazocine clearance was successful, and the model was adopted to decide the therapeutic dose of pentazocine during surgery of patients.
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