Lappin / Temple Radiotracers in Drug Development

Erscheinungsjahr 2010
ISBN: 978-1-4200-0498-4
Verlag: Taylor & Francis
Format: PDF
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 320 Seiten

Although there are numerous books on drug metabolism, Radiotracers in Drug Development is unique in explaining how radiotracers are used to elucidate a drug’s absorption, distribution, metabolism, and excretion (ADME). Covering traditional and recent technologies and applications, the book takes a strong industrial approach, discussing the basics of scintillation counting and untangling the various data processing methods often specific to individual manufacturers. The chapters include descriptions of the latest micro-plate counters and the growing applications of accelerator mass spectrometry, positron emission tomography, gamma-scintigraphy, and radioluminography. In addition to describing how the analytical technologies work, the contributors explain how the data are interpreted and used in the drug registration process. A unique reference and training aid essential for every drug metabolism department or drug metabolism research team, the book provides insight into the use and practice of ADME in a way that is both instructive and practical. Moving easily across the boundaries of biology, chemistry, and physics, this is the only comprehensive, interdisciplinary resource covering the how-tos of employing radiotracers in drug development. It provides detailed information on how the science is relevant to the registration process.

Zielgruppe

Pharmaceutical scientists in drug discovery and development, research scientists in the agrochemical, and animal health industries, and those studying xenobiotic metabolism.

Autoren/Hrsg.

Lappin, Graham

Temple, Simon

Fachgebiete

• Naturwissenschaften Biowissenschaften Toxikologie
• Technische Wissenschaften Verfahrenstechnik | Chemieingenieurwesen | Biotechnologie Pharmazeutische Technologie
• Medizin | Veterinärmedizin Medizin | Public Health | Pharmazie | Zahnmedizin Medizinische Fachgebiete Pharmakologie, Toxikologie

Inhaltsverzeichnis

Radiotracers and Drug Registration, Graham Lappin
The Drug Registration Process
Drug Metabolism
Origins of Radiotracer Studies
New Chemical Entities and Biopharmaceuticals
What Are Radiotracers Used for in Drug Registration?
Detection of Radioactivity
The Regulatory Position of Metabolism Studies
Acknowledgments
References.
Radioactivity and Radiotracers, Graham Lappin
Atoms and Isotopes
Isotope Stability
Types of Radioactive Decay
Safety
Units of Radioactivity
Units of Dose
Half-Life
Specific Activity
Maximum Theoretical Specific Activity
Universal Quantification
Calculation of Limits of Detection (LOD)
Synthesis of Radiolabeled Compounds
Radiopurity and Autoradiolysis
Kinetic Isotope Effects
Further Reading
Acknowledgments
References
The Study of Drug Metabolism Using Radiotracers, Graham Lappin
Introduction
Choice of Radiolabel
Test Systems
In Vitro Studies
In Vivo Studies: Experimental Aspects
In Vivo Studies:Data Interpretation
Structural Alerts
Appendix 1: An Overview of Xenobiotic Biotransformations
Appendix 2:Examples of Xenobiotic Metabolism Studies from the Literature
Appendix 3:Pharmacokinetics
Acknowledgments
References
DNA Binding, Isotope Dilution, and Other Uses of Radiotracers, Graham Lappin
Introduction
DNA Binding
Radioimmunoassay
Gel Blotting
Isotope Dilution
Miscellaneous Uses
References
Quantitative Whole-Body Autoradiography (QWBA), Brian Whitby
Introduction
Principles and History of QWBA
The Modern Technique of Whole-Body Autoradiography
Some Specific Uses of the QWBA Technique
Microautoradiography5.6 Summary
Appendix 1: Dosimetry Calculations for the Administration of Radioisotopes to Humans
Acknowledgment
References Scintillation Counting, Simon Temple
Introduction
How Does Scintillation Counting Work?
Photomultipliers and Accompanying Circuitry
Spectrum Analysis and the Introduction of the Multichannel Analyzer
Scintillators
Quench
Interferences in Scintillation Counting
Static
Wall Effect
Cherenkov Counting
Dual-Label Counting
Gamma Counting
ß–-Counting with Solid Scintillators
Multiwell Plate Scintillation Counting
Flow Scintillation Counting
References
Statistics in Liquid Scintillation Counting, Simon Temple
Introduction
Standard Deviation
Use of %2ó in Scintillation Counting
Low Activity Counting
Limits of Detection
References
Instrumentation for Detection of Radioactivity, Simon Temple
Introduction
History
Background Reduction
Quench Correction: General Considerations
Quench Correction without an External Standard
Methods of Quench Correction Using External Standards
Solid vs. Liquid Scintillation Counting
Microplate Scintillation Counters
Flow Scintillation Counting
Stationary Eluate Analysis
Multicell Eluate Analysis
Wire Scanners
Radioluminography
Appendix 1: List of Instrument Manufacturers and Suppliers
References
Sample Preparation for Liquid Scintillation Counting, Simon Temple
Introduction
Solubilization vs. Oxidation
General Considerations
Urine
Whole Blood and Bile
Plasma and Serum
Biological Tissues
Feces
Noncommercial Solubilizers
Acknowledgment
Biomedical Accelerator Mass Spectrometry, Graham Lappin
The Beginnings of Accelerator Mass Spectrometry
AMS Instrumentation
Isotopes
Sample Preparation
Data Handling
Sensitivity and Precision of AMS
The First Biomedical AMS Studies
AMS and Drug Development
Acknowledgments
References
Positron Emission Tomography, Barbara S. Koetz and Patricia M. Price
Introduction
General Principles of PET
Spatial Resolution and Detectors
Data Gathering and Interpretation
Isotope Generation Using a Cyclotron
Choice of Radioisotopes
Labeled Ligand and Drug Synthesis
PET Application: Pharmacokinetic Studies
Pharmacodynamic Studies
References
Gamma Scintigraphy and SPECT, Stephen P. Newman and Gary R. Pitcairn
The Development of Scintigraphic Imaging
Data Gathering and Interpretation
Applications to Formulation Design
References