A pharmacokinetic model for enterohepatic recirculation in the rat: phenolphthalein, a model drug

A classical compartmental pharmacokinetic model was developed to describe the systemic blood concentration-time profile of phenolphthalein and its glucuronide conjugate (total 3H) following a single intravenous bolus injection of [3H]phenolphthalein. The model incorporates a biliary transport system, including a finite lag time for the biliary phenophthalein glucuronide to be hydrolyzed in the intestine before absorption. Data obtained from bile duct-cannulated animals were fit to the same model excluding any component for intestinal absorption. Agreement between the rate constants obtained for both fits indicates that the model is internally consistent. The model was then used to simulate a 24-hour time-course of phenolphthalein-equivalent blood concentrations which indicates that the long apparent half-lives calculated during this period are artifacts of recirculation.