Pharmacokinetics and Toxicokinetics: 1st Edition (Hardback) book cover

Pharmacokinetics and Toxicokinetics

1st Edition

By Mehdi Boroujerdi

CRC Press

550 pages | 182 B/W Illus.

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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

About the Author

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.

Subject Categories

BISAC Subject Codes/Headings:
MAT000000
MATHEMATICS / General
MED071000
MEDICAL / Pharmacology
MED096000
MEDICAL / Toxicology