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Pharmacokinetics and Toxicokinetics




ISBN 9781482221343
Published February 24, 2015 by CRC Press
550 Pages - 182 B/W Illustrations

 
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Book Description

Pharmacokinetics and Toxicokinetics provides an overview of pharmacokinetics and toxicokinetics in a comprehensible, interrelated, and applied manner. It integrates the principles held in common by both fields through a logical and systematic approach.

The book presents mathematical descriptions of physiological processes employed in different approaches to PK/TK modeling. It focuses on emphasizing general principles and concepts, rather than isolated observations. Above all, the book is an effort to blend the pharmaceutical and toxicological aspects of both fields.

The systematic compilation of mathematical concepts and methodologies allows readers to decide on relevant concepts and approaches for their research, scientific or regulatory decisions, or for offering advance courses and seminars. This is an invaluable resource for scientists in the pharmaceutical sciences, clinical sciences, and environmental health sciences, as well as those involved in drug discovery and development.

Table of Contents

The Influence of Routes of Administration on ADME
Introduction
Pharmacokinetics (PK) and Pharmacodynamics (PD)
Toxicokinetics (TK) and Toxicodynamics (TD)
Concepts Basic to PK and TK
Influence of Routes of Exposure/Administration on PK/TK analysis
Biomarkers
References

Mechanisms of Absorption and Permeation of Xenobiotics
Introduction
Passive Diffusion
Carrier-Mediated Transcellular Diffusion
Transcellular Diffusion Subject to P-Glycoprotein EffluxActive Transport
Endocytosis and Pinocytosis
Solvent Drag, Osmosis, and Two-Pore Theory
Ion-Pair Absorption
References

In Vivo Distribution of Xenobiotics
Introduction
Factors Influencing the Distribution of Xenobiotics in the BodyReferences

Elimination Rate, Clearance and the Theoretical Models
Introduction
Rate of Elimination and Extraction Ratio
Clearance
References

Renal Excretion of Xenobiotics and Estimation of Related PK/TK Parameters and Constants
Introduction
Glomerular Filtration
Tubular Reabsorption and Secretion
Estimation of Glomerular Filtration Rate (GFR)
Analysis of Urinary Data
Renal Metabolism
Estimation of PK/TK Parameters and Constants of Elimination When Using Dialysis
References

Biotransformation of Xenobiotics
Introduction
Liver
Biotransformation (Metabolism)
In Vitro Systems for Xenobiotics Metabolism Study
In Vivo Samples for Drug Metabolism Study
References

Kinetics of In Vitro Metabolism Assimilation of Intrinsic Clearance in Hepatic Clearance
Introduction
Michaelis-Menten Kinetics
Assimilation of Intrinsic Clearance in Hepatic Clearance Using Liver Models
Inhibition of Xenobiotic Metabolism
Induction of Xenobiotic Metabolism
References

Pharmaceutical, Biopharmaceutical, and Physiological Factors Influencing Oral Absorption of Xenobiotics-Mechanistic Absorption Models
Introduction
Classification of Factors Influencing GI Tract Absorption
Mechanistic Absorption Models
References

Mathematical Modeling in Pharmacokinetics and Toxicokinetics
Introduction
Physiologically Based Pharmacokinetics Models (PBPK Models)
Compartmental Analysis—Linear Pharmacokinetics
Non-Compartmental Analysis Based on Statistical Moment Theory
PK/PD and TK/TD Modeling
Physiologically Based PK/PD or TK/TD Modeling
Hysteresis Curve
References

PK/TK Analysis of Instantaneous Exposure to Xenobiotics (Single Bolus Injection)
Introduction
Linear One-Compartment Open Model
Linear Two-Compartment Open Model with Elimination from the Central Compartment
Linear Two-Compartment Open Model with Bolus Injection in the Central Compartment and Elimination from Peripheral Compartment
Linear Three-Compartment Open Model with Bolus Injection and Elimination from Central Compartment
Linear Three-Compartment Open Model with Elimination from Peripheral Compartment
Comparing Models
References

PK/TK Analysis of Continuous Zero-Order Exposure to Xenobiotics (Intravenous Infusion)
Introduction
Compartmental Analysis
References

PK/TK Analysis of Xenobiotics Absorbed via an Extravascular Route of Administration (Oral Administration)
Introduction
Compartmental Analysis
References

PK/TK of Xenobiotics Absorbed through the Skin (Transdermal Absorption)
Introduction
Factors Influencing the Transdermal Absorption of Xenobiotics
Mathematical Model for Prediction of Skin Concentration
PK/TK of Percutaneous Absorption
References

PK/TK Analysis of Multiple Dosing
Introduction
Kinetics of Multiple Intravenous Bolus Injections—One-Compartment Model
Kinetics of Multiple Oral Administration
Effect of Changing Dose, Dosing Interval, and Half-Life on Accumulation in the Body and Fluctuation of Plasma Concentration
Effect of Irregular Dosing Interval on the Plasma Concentration of Multiple-Dosing Regimen
Multiple Dosing Kinetics—Two-Compartment Model
Multiple Intravenous Infusions
References

Bioavailability, Bioequivalence, and Biosimilar Evaluations
Introduction
Peak Exposure, Total Exposure, and Early Exposure
Bioavailability and First-Pass Metabolism
Confirmation of Linearity of Relative and Absolute Bioavailability during Multiple Dosing Regimen
Bioequivalence Study
Biosimilars (Biosimilarity and Interchangeability)
References

Preclinical PK/TK and Clinical Trials
Introduction
Preclinical PK/TK
PK/TK and Clinical Trials
Dose and Dosing Regimen Adjustment for Patients with Variable Renal Impairments in Clinical Trials
References

Population Pharmacokinetics/Toxicokinetics
Introduction
Fixed Effect and Random Effect Parameters
Linear and Nonlinear Mixed-Effects Models
PLME Model
Naïve-Pooled Data Approach (NPD)
Two-Stage Approach
Bayesian Approach
Tools of Computational Statistics for PPK
References

Quantitative Extrapolation Interspecies Scaling/Low Dose Extrapolation
Introduction
Interspecies Scaling in Mammals
Toxicogenomics
Low Dose Extrapolation
References

Appendix A: Relevant Mathematical Concepts

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Author(s)

Biography

Mehdi Boroujerdi is a professor of pharmaceutical sciences and the founding dean of the School of Pharmacy at the University of Massachusetts Lowell. He previously served as a professor, dean and provost of the Albany College of Pharmacy and Health Sciences in New York. He earned his PhD in pharmaceutics and pharmacokinetics from the University of North Carolina at Chapel Hill and conducted postdoctoral research at the National Institutes of Health – National Institute of Environmental Health Sciences (NIH-NIEHS) in chemical carcinogenesis and low-dose extrapolation. Dr. Boroujerdi has a broad background and experience in pharmacokinetics/toxicokinetics and the role of influx and efflux proteins. His current research explores the chemoresistance of pancreatic cancer cells to chemotherapeutic agents both in cell culture and in vivo. He has published more than 110 peer-reviewed articles as well as a textbook on pharmacokinetics, principles, and applications.