This article was submitted as an invited paper resulting from the “Understanding Complex Systems” conference held at the University of Illinois at Urbana-Champaign, May 2007.
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Research Article
Evaluating an hepatic enzyme induction mechanism through coarse- and fine-grained measurements of an in silico liver†
Article first published online: 17 OCT 2008
DOI: 10.1002/cplx.20253
Copyright © 2008 Wiley Periodicals, Inc.
Additional Information
How to Cite
Ropella, G. E. P., Park, S. and Hunt, C. A. (2009), Evaluating an hepatic enzyme induction mechanism through coarse- and fine-grained measurements of an in silico liver. Complexity, 14: 28–34. doi: 10.1002/cplx.20253
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Publication History
- Issue published online: 1 JUL 2009
- Article first published online: 17 OCT 2008
- Manuscript Accepted: 7 AUG 2008
- Manuscript Received: 26 SEP 2007
- Abstract
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Keywords:
- agent-based;
- multi-agent;
- complex system;
- modeling and simulation;
- systems biology;
- pharmacokinetics;
- hepatic clearance;
- enzyme induction
Abstract
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 EI 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. © 2008 Wiley Periodicals, Inc. Complexity, 2009