Bucher, Joachim and Riedmaier, Stephan and Schnabel, Anke and Marcus, Katrin and Vacun, Gabriele and Weiss, Thomas S. and Thasler, Wolfgang E. and Nüssler, Andreas K. and Zanger, Ulrich M. and Reuss, Matthias
A systems biology approach to dynamic modeling and inter-subject variability of statin pharmacokinetics in human hepatocytes.
BMC systems biology 5 (1), p. 66.
A dynamic model for the biotransformation of atorvastatin has been developed using quantitative metabolite measurements in primary human hepatocytes. The model comprises kinetics for transport processes and metabolic enzymes as well as population liver expression data allowing us to assess the impact of inter-individual variability of concentrations of key proteins. Application of computational tools for parameter sensitivity analysis enabled us to considerably improve the validity of the model and to create a consistent framework for precise computer-aided simulations in toxicology.