The liver is the largest and most important organ of biotransformation in the human organism. Because of its central place between the gastrointestine and the systemic circulation the liver determines the bioavailability of orally applied drugs. The variety of its tasks is made possible by a complex and heterogeneous structure whose essential components should be modelled as realistically as possible. Previous investigations have revealed, that the choice of the model has an essential influence on the estimation of the permeability of the liver in case of extensive metabolised drugs. The aim of the thesis was firstly the extension of a permeation-diffusion model (WEISS AND ROBERTS), which earlier was only available for non-eliminating organs, and secondly validating investigations of the new model. The permeation-diffusion model is based on a stochastic two-phase model, which reflects the microscopic structure of the liver: capillary vessel and interstitium (inner phase) surrounded by a single layer of liver cells (outer phase). Moreover this model makes possible a flexible modelling of an intravasculare mixture caused by an extensive branched capillary system. Known liver models (compartment, tube and dispersion model) are special cases of the extended permeation-diffusion model. The often used dispersion model and its inherent inverse Gaussian function was proved to be inflexible in describing the concentration time profile of intravascular markers found in experiments with perfused rat livers. Instead of this, the empirically proposed weighted sum of two inverse Gaussian functions (WEISS UND ROBERTS) is suited for the description of the data. Simulations show, that the model misspecification of the intravascular model may falsify the parameter estimations of the tissue distribution parameters of the permeation-diffusion model. Slow intracellular diffusion effects the transit time distribution dependent on the parameter constellations, not only quantitatively but also qualitatively, and are reflected by a raised liver permeability and prolonged mean transit time if elimination occurs. The first indications on the validity of the extended permeation-diffusion model revealed the fit of the kinetics of several phenol derivates. The new model described the experimental data well and was superior to the dispersion model. Investigations on the sensitivity of the parameter estimations, the large vessels of the liver, and a bioavailability study complemented the model validation.