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.
Hunt
C
C
Dept of Bioengineering and Therapeutic Sciences, BioSystems Group, University of California, San Francisco, CA 94143, USA. a.hunt@ucsf.edu
Ropella
Glen E P
GE
D002627:Chemistry, Physical; D003198:Computer Simulation; D003201:Computers; D004347:Drug Interactions; D006801:Humans; D008099:Liver / Q000033:anatomy & histology / Q000201:enzymology*; D008102:Liver Circulation; D015233:Models, Statistical; D008962:Models, Theoretical; D009010:Monte Carlo Method; D016571:Neural Networks, Computer; D010641:Phenotype; D012984:Software; D013997:Time Factors