Evaluating an Hepatic Enzyme Induction Mechanism through Coarse- and Fine-Grained Measurements of an In Silico Liver

Results from simulation experiments falsified the hypothesis that a uniform distribution of simulated drug passing through an in silico liver (ISL) will produce a uniform extent of enzyme induction (EI). Wet-lab El experiments, as formulated, are infeasible. The simulated EI is intended to have a hepatic counterpart. The ISL is synthetic, physiologically based, fine-grained., and multi-agent. It has been validated against in situ drug disposition data. We discuss methodological considerations regarding the phenomenal manifold, multi-level observation, and manipulation of synthetic models and their referents. Interestingly, a lower probability of metabolism caused higher EI and, counter-intuitively, more extraction. (C) 2008 Wiley Periodicals, Inc. Complexity 14: 28-34, 2009