43. Physiologically Based Pharmacokinetic Modeling: Inhalation, Ingestion, and Dermal Absorption

  1. Ene I. Ette3,4 and
  2. Paul J. Williams5,6
  1. Sastry S. Isukapalli1,
  2. Amit Roy2 and
  3. Panos G. Georgopoulos1

Published Online: 18 MAY 2006

DOI: 10.1002/9780470087978.ch43

Pharmacometrics: The Science of Quantitative Pharmacology

Pharmacometrics: The Science of Quantitative Pharmacology

How to Cite

Isukapalli, S. S., Roy, A. and Georgopoulos, P. G. (2007) Physiologically Based Pharmacokinetic Modeling: Inhalation, Ingestion, and Dermal Absorption, in Pharmacometrics: The Science of Quantitative Pharmacology (eds E. I. Ette and P. J. Williams), John Wiley & Sons, Inc., Hoboken, NJ, USA. doi: 10.1002/9780470087978.ch43

Editor Information

  1. 3

    Clinical Pharmacology, Vertex Pharmaceuticals, 130 Waverly St., Cambridge, MA 02139, USA

  2. 4

    Anoixis Corp., 214 N. Main St., Natick, MA 01760, USA

  3. 5

    Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Stockton, CA 95211, USA

  4. 6

    Anoixis Corp., 1918 Verdi Ct., Stockton CA 95207, USA

Author Information

  1. 1

    Computational Chemodynamics Laboratory, Environmental and Occupational Health Sciences Institute, 70 Frelinghuysen Road, Piscataway, NJ 08854, USA

  2. 2

    Strategic Modeling and Simulation, Bristol-Myers Squibb, Route 206 and Provinceline Road, Princeton, NJ 08540, USA

Publication History

  1. Published Online: 18 MAY 2006
  2. Published Print: 23 MAR 2007

ISBN Information

Print ISBN: 9780471677833

Online ISBN: 9780470087978

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Keywords:

  • Physiologically Based Pharmacokinetic (PBPK) modeling;
  • PBPK model structure;
  • model parameters;
  • physiological parameters;
  • partition coefficients;
  • biotransformation parameters;
  • PBPK model implementation;
  • PBPK model evaluation;
  • PBPK model refinement;
  • sensitivity;
  • uncertainty analysis;
  • variability analysis;
  • model parameter estimation

Summary

This chapter presents an introduction to physiologically based pharmacokinetic (PBPK) modeling, and describes the typical steps in the development of a PBPK model. These steps include determination of model structure, implementation of the model, and specification of model parameters, either through existing data sources, or by parameter estimation. These steps are illustrated using a PBPK model for chloroform as an example. This model predicts the concentration-time profiles of chloroform in selected tissues following inhalation, ingestion, or dermal absorption of chloroform. The example is presented in a tutorial manner, presenting the theoretical basis for the model along with cross-references to the corresponding Matlab code. This code is written in a manner that allows alterations in the number of selected tissues, with minor changes to a configuration file. The model structure and the code are directly applicable to other volatile organic compounds, and can be adapted in a relatively straightforward manner for other xenobiotics.