Model systems for pharmacokinetics of steroid drugs subject to enterohepatic circulation

Abstract

A number of drugs including steroid hormones undergo enterohepatic circulation (EHC) which influences the drug disposition parameters. EHC of drugs leads to prolonged drug exposition which may enhance the risk of liver incompatibility. The extent of EHC expressed by the reabsorption rate of a given drug is of interest from the clinical and toxicological point of view. A two-compartment model with an additional time lag was realized by a hybrid computer system to study the influence of EHC on the shape of plasma concentration-time profiles and pharmacokinetic parameters. Reabsorption rates of potential steroid drugs were calculated by model-simulation and the results compared with the experimentally found ones. Although the lag time model is only a simplified approximation to the underlying physiological processes it reflects sufficiently the pharmacokinetic profile of steroid drugs subject to EHC.