Corrigendum to ’Development of a mechanistic biokinetic model for hepatic bile acid handling to predict possible cholestatic effects of drugs’ [European Journal of Pharmaceutical Sciences 115 (2018) 175-184] (S0928098718300071) (10.1016/j.ejps.2018.01.007))

The authors regret the molar unit is incorrectly displayed on the x-axis in Fig. 4A and 4C and on the y-axis in Fig. 4B, 4D and Fig. 5. The correct versions of the figures are displayed below together with the unchanged legends. The authors would like to apologise for any inconvenience caused. DOI of original article: 10.1016/j.ejps.2018.01.007 ...

Development of a mechanistic biokinetic model for hepatic bile acid handling to predict possible cholestatic effects of drugs

Drug-induced liver injury (DILI) is a common reason for drug withdrawal from the market. An important cause of DILI is drug-induced cholestasis. One of the major players involved in drug-induced cholestasis is the bile salt efflux pump (BSEP; ABCB11). Inhibition of BSEP by drugs potentially leads to cholestasis due to increased (toxic)...

The consequence of regional gradients of P-gp and CYP3A4 for drug-drug interactions by P-gp inhibitors and the P-gp/CYP3A4 interplay in the human intestine ex vivo

Intestinal P-gp and CYP3A4 work coordinately to reduce the intracellular concentration of drugs, and drug-drug interactions (DDIs) based on this interplay are of clinical importance and require pre-clinical investigation. Using precision-cut intestinal slices (PCIS) of human jejunum, ileum and colon, we investigated the P-gp/CYP3A4 interplay and...

Viability, function and morphological integrity of precision-cut liver slices during prolonged incubation: Effects of culture medium

Precision-cut liver slices (PCLS) are an ex vivo model for metabolism and toxicity studies. However, data on the maintenance of the morphological integrity of the various cell types in the slices during prolonged incubation are lacking. Therefore, our aims were to characterize morphological and functional changes in rat PCLS during five days of...

Evaluation of research activities and research needs to increase the impact and applicability of alternative testing strategies in risk assessment practice

The present paper aims at identifying strategies to increase the impact and applicability of alternative testing strategies in risk assessment. To this end, a quantitative and qualitative literature evaluation was performed on (a) current research efforts in the development of in vitro methods aiming for alternatives to animal testing, (b) the...

Comparison of five incubation systems for rat liver slices using functional and viability parameters

Precision-cut liver slices are presently used for various research objects, e.g. to study metabolism, transport, and toxicity of xenobiotics. Various incubation systems are presently employed, but a systematic comparison between these incubation systems with respect to preservation of slice function has not been performed yet. Therefore, we...