Physiologically Based Pharmacokinetic Modeling
Science and Applications
1. Edition July 2005
440 Pages, Hardcover
Handbook/Reference Book
Short Description
This book describes the development of physiologically-based pharmacokinetics (PBPK) modeling for toxic compounds over the past eight decades as well as the current uses of these models. It reviews PBPK model results for various classes of compounds with coverage of historical development, specific modeling challenges and current practices. Readers will also find discussions on the use of these PBPK models to support pharmacodynamic modeling for toxic responses and future directions for modeling.
A definitive, single source of information on PBPK modeling
Physiologically-based pharmacokinetic (PBPK) modeling is becoming increasingly important in human health risk assessments and in supporting pharmacodynamic modeling for toxic responses. Organized by classes of compounds and modeling purposes so users can quickly access information, this is the first comprehensive reference of its kind.
This book presents an overview of the underlying principles of PBPK model development. Then it provides a compendium of PBPK modeling information, including historical development, specific modeling challenges, and current practices for:
* Halogenated Alkanes
* Halogenated Alkenes
* Alkene and Aromatic Compounds
* Reactive Vapors in the Nasal Cavity
* Alkanes, Oxyhydrocarbons, and Related Compounds
* Pesticides and Persistent Organic Pollutants
* Dioxin and Related Compounds
* Metals and Inorganic Compounds
* Drugs
* Antineoplastic Agents
* Perinatal Transfer
* Mixtures
* Dermal Exposure Models
In addition to pinpointing specific information, readers can explore diverse modeling techniques and applications. An authoritative reference for toxicologists, ecotoxicologists, risk assessors, regulators, pharmacologists, pharmacists, and graduate students in pharmacokinetics and toxicology, Physiologically-Based Pharmacokinetic Modeling compiles information from leaders in the field and discusses future directions for PBPK modeling.
Chapter 1.Introduction: A Historical Perspective of the Development and Applications of PBPK Models.
1. Introduction.
2. A Historical Perspective.
3. Expansion of PBPK Model Applications.
4. Summary.
SECTION 1. PBPK MODELING FOR VOLATILE ORGANIC COMPOUNDS.#
Chapter 2. Halogenated Alkanes.
1. Introduction.
2. PBPK Model Development for Volatile Organics.
3. Advances in Experimental Methods Demonstrated for Groups of Chemicals.
4. PBPK Models for Halogenated Alkanes.
5. Summary.
Chapter 3. Halogenated Alkenes.
1. Introduction.
2. The Chloroethylenes: Background.
3. Review of PBPK Models.
4. Summary.
Chapter 4. Alkene and Aromatic Compounds.
1. Introduction.
2. PK and Pharmacodynamic Properties Important in PBPK Model Development for Aromatic and Alkene Compounds.
3. Review of Aromatic and Alkene PBPK Models.
4. Summary.
Chapter 5. Reactive Vapors in the Nasal Cavity.
1. Introduction.
2. No Air-Phase Models.
3. Creating the Air Phase Compartments.
4. Other Models for Vapors Affecting Nasal Tissues.
5. Methyl Methacrylate.
6. Formaldehyde.
7. Hydrogen Sulfide.
10. Summary.
Chapter 6. Alkanes, Oxyhydrocarbons and Related Compounds.
1. Introduction.
2. Purposes for PBPK Model Development.
3. PBPK Models for Four Classes of Compounds.
4. Summary.
SECTION 2. PBPK MODEL DEVELOPMENT FOR ENVIRONMENTAL POLLUTANTS.
Chapter 7. Pesticides and Persistent Organic Pollutants (POPs).
1. Introduction.
2. Pesticides.
3. Polychlorinated and Polybrominated Biphenyls, PCBs and PBBs.
4. Summary.
Chapter 8. Dioxin and Related Compounds.
1. Introduction.
2. Toxicity.
3. Mode of Action.
4. Pharmacokinetics.
5. PBPK Models of TCDD.
6. Summary.
Chapter 9. Metals and Inorganic Compounds.
1. Introduction.
2. Physiologically Based Modeling of Metals.
3. PBPK Models for Non-Metals.
4. Compartmental Models for Miscellaneous Inorganic and/or Endogenous Chemicals.
5. Research Needs.
6. Summary.
SECTION 3. PHARMACEUTICAL APPLICATIONS OF PBPK MODELS.
Chapter 10. Drugs.
1. Introduction.
2. Describing the Tissue Distribution of Drugs.
3. Describing Metabolism and Other Clearance Processes of Drugs.
4. Other Issues in Model Development for Drugs.
5. Future Perspectives.
6. Summary.
Chapter 11. Antineoplastic Agents.
1. Introduction.
2. PBPK Models for Antineoplastic Agents.
3. Summary.
SECTION 4. PBPK MODELING APPROACHES FOR SPECIAL APPLICATIONS.
Chapter 12. Perinatal Transfer.
1. Introduction.
2. Physiological and Biochemical Changes During Pregnancy.
3. Physiological Factors Incorporated into PBPK Models for Perinatal Pharmacokinetics.
4. PBPK Models for Perinatal Transfer.
5. Risk Assessment Dosimetry Models.
6. Summary.
Chapter 13. Mixtures.
1. Introduction.
2. PBPK Modeling Of Chemical Mixtures.
3. Future Perspectives: Second Generation PBPK/PD modeling.
4. Summary.
Chapter 14. Dermal Exposure Models.
1. Introduction.
2. Factors to Consider in Modeling Dermal Absorption.
3. Dermal Absorption Models.
4. Experimental Methods.
5. Summary.
Chapter 15. Conclusions and Future Directions.
1. Introduction.
2. A Systems Approach for Pharmacokinetics.
3. Modeling Both Dose and Response.
4. Opportunities for PBPK Modeling in Pharmaceutical Industry.
5. Reaction Network Modeling with Xenobiotics.
6. Systems Biology and Dose-Response.
7. Summary.
MICAELA B. REDDY, PhD, is a research professor at CETT where she has developed PBPK models for risk assessment and toxicology applications.
RAYMOND S. H. YANG, PhD, Professor of Toxicology and former director, CETT, championed applications of PBPK modeling in research on the toxicology of chemical mixtures.
HARVEY J. CLEWELL III, MS, Director, Center for Human Health Assessment, CIIT Centers for Health Research, Research Triangle Park, North Carolina, played a major role in the first uses of PBPK modeling in cancer and non-cancer risk assessments by several federal agencies, including EPA, ATSDR, OSHA, and FDA.
MELVIN E. ANDERSEN, PhD, a pioneer in use of PBPK modeling in toxicology and risk assessment, is Director, Computational Biology Division, CIIT Centers for Health Research, Research Triangle Park, North Carolina.
