Using an in silico liver to evaluate a hepatic enzyme induction mechanism

Will enzyme induction (EI) within different hepatic lobular zones, following initial exposure to a single xenobiotic, be homogeneous or heterogeneous? Wet-lab EI experiments, as formulated, are infeasible. The In Silico Liver (ISL) was designed in part to explore plausible answers to such questions. The ISL is synthetic, physiologically based, fine-grained, and multi-agent. It has been validated against in situ drug disposition data. Results from simulation experiments falsified the hypothesis that a uniform distribution of simulated drug passing through an ISL will produce uniform EI. The results may have a hepatic counterpart. We discuss methodological considerations regarding multi-level observation and manipulation of livers and this new class of models.