Physiologically based kinetic model for cardiotoxicity prediction
October 2021
Wageningen University and Research, Wageningen, Netherlands
In this study, the applicability of an invitro-in silico approach to predict human cardiotoxicity of the herbal alkaloid ibogaine and its metabolite noribogaine were investigated. Physiologically based kinetic (PBK) models were developed using in silico-derived parameters and biokinetic data obtained from in vitro human liver microsomal incubations and human colorectal cells (Caco-2) transport studies. Human induced pluripotent stem cell-derived cardiomyocytes combined with a multi-electrode array assay were used to determine in vitro concentration-dependent cardiotoxicity. To evaluate the model, the results were compared with the human in vivo data reported in clinical studies. A comparison of the predictions with the available in vivo data demonstrated the adequate performance of the developed model.
A new approach methodology (NAM) for the prediction of (nor)ibogaine-induced cardiotoxicity in humans
Ivonne M. C. M. Rietjens
Added on: 04-22-2022
[1] https://www.altex.org/index.php/altex/article/view/2282
