A pharmacokinetic model for analysis of drug disposition profiles undergoing enterohepatic circulation

Abstract

Abstract A new and simple pharmacokinetic model that can explain enterohepatic circulation profiles for both single and repeated dosing was developed, and its applicability and usefulness were assessed by an actual published data set and simulation study. The model is basically a conventional compartment model, and the transfer rate from the bile compartment to the central compartment is assumed to change periodically, with the sine function being used to describe this periodical change. Using this model, the effect of the parameter values on plasma time-course profiles was examined by simulation, and the applicability of the model was tested by curve fitting to obtain the parameter estimates using an actual published data set. These studies confirmed that our model can simulate the periodical increase of the concentration due to re-absorption. By averaging the sine function in the transfer rate from the bile compartment to the central compartment, a smoothed time-course profile in the elimination phase that is independent of the enterohepatic cycle can be obtained. Also, the apparent half-life in the elimination phase can be estimated, which is useful especially for evaluating drug accumulation during repeated dosing. It was suggested that the present model can be used to evaluate the drug disposition profile with enterohepatic circulation. The effects of sampling points and sampling time on parameter estimation are also discussed.