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Systems Toxicology Modeling for Prediction in Humans

Systems Toxicology

Image Analysis, Sequencing and Systems Modeling

  1. Cristiano Migliorini1,
  2. Thierry Lave1,
  3. Neil J. Parrott1,
  4. Micaela Reddy1,
  5. Hans Peter Grimm1,
  6. Robert C. Penland2,
  7. Antoine Soubret2,
  8. Gabriel Helmlinger2,
  9. Anna Georgieva2,
  10. Klaas P. Zuideveld1

Published Online: 15 SEP 2011

DOI: 10.1002/9780470744307.gat233

General, Applied and Systems Toxicology

General, Applied and Systems Toxicology

How to Cite

Migliorini, C., Lave, T., Parrott, N. J., Reddy, M., Grimm, H. P., Penland, R. C., Soubret, A., Helmlinger, G., Georgieva, A. and Zuideveld, K. P. 2011. Systems Toxicology Modeling for Prediction in Humans. General, Applied and Systems Toxicology. .

Author Information

  1. 1

    F. Hoffmann-La Roche, Ltd., Basel, Switzerland

  2. 2

    Novartis Institutes for Biomedical Research, Cambridge, MA, USA

Publication History

  1. Published Online: 15 SEP 2011

Abstract

This chapter aims to illustrate the ability of physiologically based mechanistic mathematical models to predict pharmacokinetics and toxicity across species. The underlying principle is that toxicity must be interpreted in the physiological context where it is measured.

Various methodologies for predicting the pharmacokinetics, QT prolongation and proarrhythmic risk are evaluated. Finally an integration of both pharmacokinetics and toxicokinetics in chemotherapy-induced neutropenia is discussed. It is believed that the methodologies presented for integrating available knowledge across experiments to predict toxicology in humans will ultimately make drug development more efficient, cost cost-effective, and socially more acceptable.

Keywords:

  • pharmacokinetics;
  • PBPK;
  • toxicokinetics;
  • QT prolongation;
  • cardiac;
  • electrophysiology;
  • myelosuppression;
  • neutropenia