Pharmacokinetic study of the enterohepatic circulation of acetaminophen glucuronide in rats

A pharmacokinetic model of the enterohepatic circulation of acetaminophen glucuronide was investigated in rats with particular attention to a lag time between biliary excretion and reabsorption. The plasma drug data obtained after acetaminophen glucuronide injection into the various sites of the gut confirmed that there is a lag time in the enterohepatic circulation and that the lag time is due to the intestinal transit period of the conjugate to the site of the hydrolysis. The value of the lag time was fairly close to that reported previously in the rat. Based on the result, a compartment model with periodic trigonometric function for the enterohepatic circulation was built up and the urinary excretion data were fitted to this model. Same parameters which are considered to be common to other glucuronide conjugates were in good agreement with those reported previously, indicating that the model and those values are useful to study the enterohepatic circulation for glucuronides of other compounds in the rat.