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E-grāmata: Handbook of Bioanalysis and Drug Metabolism

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  • Formāts: 408 pages
  • Izdošanas datums: 08-Oct-2021
  • Izdevniecība: CRC Press
  • Valoda: eng
  • ISBN-13: 9781134477371
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Handbook of Bioanalysis and Drug MetabolismPalielināt
  • Formāts: 408 pages
  • Izdošanas datums: 08-Oct-2021
  • Izdevniecība: CRC Press
  • Valoda: eng
  • ISBN-13: 9781134477371
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Techniques, methodology, and theory of bioanalysis, pharmacokinetics, and metabolism are examined from the perspective of scientists working on research and development in the pharmaceutical industry, in this handbook for senior undergraduates and postgraduates studying drug metabolism in courses such as pharmaceutical science, physiology, and toxicology. Coverage includes sample preparation, mass spectrometry and quantitative bioanalysis, pre-clinical pharmacokinetics, and whole body autoradiography, as well as in vitro techniques for investigating drug metabolism, and identification of drug metabolites in biological fluids using spectroscopic and chromatographic techniques. Evans has 25 years of experience in research and development in the pharmaceutical industry. Annotation ©2004 Book News, Inc., Portland, OR (booknews.com)

Recent years have seen a greater industrial emphasis in undergraduate and postgraduate courses in the pharmaceutical and chemical sciences. However, textbooks have been slow to adapt, leaving cohorts of students without a reference text to take into the industrial setting - until now. This stimulating new handbook examines the techniques, methodology and theory of bioanalysis and drug metabolism from the perspective of scientists with extensive professional experience in drug discovery and development. It covers topics such as high performance liquid chromatography, protein binding, pharmacokinetics and drug--drug interactions. A Handbook of Bioanalysis and Drug Metabolism is an invaluable guide to senior undergraduates and postgraduates studying drug metabolism in courses such as pharmaceutical science, pharmacology, chemistry, physiology and toxicology - especially those considering industrial placements or a career in the biotechnology industry.

Editor's preface xiii
Preface xiv
Grieves Harnby: In memoriam xv
CHAPTER 1 INTRODUCTION 1(7)
Gary Evans
1.1 Bioanalysis, pharmacokinetics and drug metabolism (BPDM)
1(1)
1.2 The role of BPDM in drug discovery and drug development
2(6)
CHAPTER 2 THE IMPORTANCE OF THE PHYSICOCHEMICAL PROPERTIES OF DRUGS TO DRUG METABOLISM 8(24)
David Spalding
2.1 Introduction
8(1)
2.2 The physicochemical nature of drug molecules
9(1)
2.3 The structure of the cell membrane and its implications for drug disposition
10(1)
2.4 Drug partitioning across membranes
11(2)
2.5 The ionisation of drugs
13(4)
2.6 The pH environment of the body and how it affects drug absorption and distribution
17(3)
2.7 The importance of the physicochemical properties of drugs to their metabolism and excretion
20(4)
2.8 Chirality and its effects on drug absorption, metabolism and excretion
24(3)
2.9 The importance of physicochemical properties to the analysis of drugs
27(2)
2.10 Summary
29(1)
2.11 Bibliography
29(3)
CHAPTER 3 SAMPLE PREPARATION 32(13)
Bob Biddlecombe and Glenn Smith
3.1 Introduction
32(1)
3.2 Sample preparation techniques
32(3)
3.3 Instrumentation
35(1)
3.4 Bioanalytical automation strategy
36(6)
3.5 Future development
42(1)
3.6 References
43(2)
CHAPTER 4 HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY IN PHARMACEUTICAL BIOANALYSIS 45(24)
David N. Mallett
4.1 Introduction
45(1)
4.2 A brief look at the theory of chromatographic separation in HPLC
46(3)
4.3 The basic equipment comprising a modern HPLC system
49(8)
4.4 Modes of liquid chromatography
57(7)
4.5 High-throughput bioanalysis
64(1)
4.6 Chiral HPLC
65(1)
4.7 Future trends in HPLC
66(2)
4.8 Bibliography
68(1)
CHAPTER 5 MASS SPECTROMETRY AND QUANTITATIVE BIOANALYSIS 69(21)
Bob Biddlecombe, Sheryl Callejas and Gary Evans
5.1 Introduction
69(1)
5.2 The instruments
70(1)
5.3 Analytical interfaces
70(3)
5.4 Ionisation
73(2)
5.5 Mass analysers
75(1)
5.6 Use of MS in quantitative LC-MS
76(1)
5.7 Developing an LC-MS assay method
77(12)
5.8 Bibliography
89(1)
CHAPTER 6 IMMUNOASSAY IN PHARMACOKINETIC AND PHARMACODYNAMIC BIOANALYSIS 90(23)
Richard Nicholl, Paul Linacre and Bill Jenner
6.1 Summary
90(1)
6.2 The role of immunoassay in drug discovery and development
91(1)
6.3 Principles of immunoassay
92(3)
6.4 Assay development
95(1)
6.5 Production of reagent antibodies
95(1)
6.6 Selection and production of label
96(2)
6.7 Assay development and optimisation
98(1)
6.8 Assay validation
99(1)
6.9 Immunoassays developed in-house
100(2)
6.10 Commercial kit immunoassay
102(1)
6.11 Data handling
103(1)
6.12 Automation
103(2)
6.13 Biomarkers
105(2)
6.14 Case study: determination of COX-2 selectivity in human blood
107(1)
6.15 Biological drugs
108(4)
6.16 References
112(1)
CHAPTER 7 PRE-CLINICAL PHARMACOKINETICS 113(19)
Sheila Schwartz and Tony Pateman
7.1 Introduction
113(2)
7.2 Pharmacokinetic parameters
115(1)
7.3 Bioavailability
115(1)
7.4 Calculation of pharmacokinetic parameters
116(4)
7.5 Parameter derivations
120(5)
7.6 Study design and data handling in pre-clinical drug development
125(2)
7.7 Application of PK in drug discovery
127(2)
7.8 Interspecies scaling
129(2)
7.9 References
131(1)
CHAPTER 8 PHARMACOKINETIC/PHARMACODYNAMIC MODELLING IN PRE-CLINICAL DRUG DISCOVERY 132(10)
Tony Pateman
8.1 The importance of pharmacokinetic/pharmacodynamic modelling
132(1)
8.2 Advantages of incorporating PK/PD modelling in the drug discovery process
133(1)
8.3 PK/PD in the drug discovery process
134(2)
8.4 Principles of PK/PD modelling
136(4)
8.5 Summary
140(1)
8.6 References
141(1)
CHAPTER 9 TOXICOKINETICS 142(14)
Sheila Schwartz
9.1 Introduction
142(1)
9.2 Study design
143(3)
9.3 PK parameters for toxicokinetic evaluation
146(3)
9.4 Reporting
149(1)
9.5 Application of toxicokinetic data
150(1)
9.6 Toxicokinetic-toxicodynamic relationships
151(1)
9.7 Dose- and time-dependencies
152(3)
9.8 References
155(1)
CHAPTER 10 PROTEIN BINDING IN PLASMA: A CASE HISTORY OF A HIGHLY PROTEIN-BOUND DRUG 156(20)
Robert J. Barneby and Marco Bottacini
10.1 Introduction
156(1)
10.2 The protein binding equilibrium
157(1)
10.3 Determinants of the unbound fraction
157(1)
10.4 Principal plasma binding proteins
158(4)
10.5 The importance of protein binding in drug development
162(4)
10.6 Techniques for measurement: a brief review of the more popular techniques including advantages and disadvantages
166(2)
10.7 GV150526A: a case history of a highly bound drug
168(7)
10.8 References
175(1)
CHAPTER 11 ISOTOPE DRUG STUDIES IN MAN 176(15)
Graeme Young, John Ayrton and Tony Pateman
11.1 Radiolabelled studies in man
176(5)
11.2 Which isotope?
181(1)
11.3 Calculations
181(5)
11.4 Accelerator mass spectrometry
186(3)
11.5 Future of AMS
189(1)
11.6 Stable isotope studies
190(1)
11.7 Acknowledgements
190(1)
11.8 References
190(1)
CHAPTER 12 WHOLE BODY AUTORADIOGRAPHY 191(17)
Lee Crossman, Kenneth Brouwer and Jeanne Jarrett
12.1 Introduction
191(1)
12.2 Historical background
192(1)
12.3 Methodology
192(1)
12.4 Study design
193(1)
12.5 Obtaining whole body sections
194(1)
12.6 Imaging
195(1)
12.7 Quantitative whole body autoradiography
196(1)
12.8 Applications of quantitative whole body autoradiography
197(9)
12.9 References
206(2)
CHAPTER 13 PHASE I METABOLISM 208(14)
Peter Eddershaw and Maurice Dickins
13.1 Introduction
208(1)
13.2 Cytochrome P450s
209(6)
13.3 Monoamine oxidases (MAO)
215(1)
13.4 Flavin monooxygenases (FMO)
216(2)
13.5 Alcohol dehydrogenases (ADH) and aldehyde dehydrogenases (ALDH)
218(1)
13.6 Molybdenum hydroxylases
218(3)
13.7 Conclusions
221(1)
CHAPTER 14 PHASE II ENZYMES 222(22)
Gary Manchee, Maurice Dickins and Elizabeth Pickup
14.1 Introduction
222(1)
14.2 Phase II enzyme reactions
223(9)
14.3 Nomenclature of phase II enzymes
232(4)
14.4 Phase II enzymes and drug development
236(5)
14.5 Summary
241(1)
14.6 References
242(2)
CHAPTER 15 IN VITRO TECHNIQUES FOR INVESTIGATING DRUG METABOLISM 244(25)
Graham Somers, Peter Mutch and Amanda Woodrooffe
15.1 Introduction
244(3)
15.2 Preparation of liver subcellular fractions and hepatocytes
247(7)
15.3 Use of subcellular fractions, hepatocytes and liver slices to study drug metabolism
254(2)
15.4 In vitro-in vivo correlations
256(2)
15.5 Advantages and disadvantages of the in vitro systems used to study drug metabolism
258(3)
15.6 The study of drug interactions using in vitro systems
261(5)
15.7 References
266(3)
CHAPTER 16 DRUG-DRUG INTERACTIONS: AN IN VITRO APPROACH 269(23)
D.M. Cross and M.K. Bayliss
16.1 Introduction
269(1)
16.2 Clinical background
270(1)
16.3 The impetus behind an in vitro approach
270(1)
16.4 The mechanism behind drug-drug interactions
271(1)
16.5 Drug-metabolising enzymes
272(1)
16.6 Drug transport systems
273(1)
16.7 Plasma protein binding
274(1)
16.8 Drug concentration effects
275(1)
16.9 Inhibition of drug-metabolising enzymes and its effect
275(5)
16.10 Induction of drug-metabolising enzymes and its effect
280(1)
16.11 In vitro approaches to investigating drug interaction
281(5)
16.12 A regulatory perspective
286(1)
16.13 Some brief case histories
286(3)
16.14 Overview
289(1)
16.15 References
290(2)
CHAPTER 17 IDENTIFICATION OF DRUG METABOLITES IN BIOLOGICAL FLUIDS USING QUALITATIVE SPECTROSCOPIC AND CHROMATOGRAPHIC TECHNIQUES 292(33)
G.J. Dear and I. M. Ismail
17.1 Introduction
292(1)
17.2 Mass spectrometry
293(1)
17.3 Sample preparation
294(1)
17.4 Phase I
295(6)
17.5 Phase II
301(9)
17.6 NMR spectroscopy
310(4)
17.7 Characterisation of metabolites by 1H NMR
314(8)
17.8 '9F NMR metabolite profiling
322(1)
17.9 Conclusions
322(3)
CHAPTER 18 MOLECULAR BIOLOGY 325(34)
Steve Hood
18.1 Introduction
325(1)
18.2 Basic molecular biology
325(4)
18.3 Which enzyme?
329(1)
18.4 Expressed enzymes
329(12)
18.5 Induction or suppression?
341(8)
18.6 Population genetics and polymorphisms
349(3)
18.7 References
352(6)
18.8 Bibliography
358(1)
CHAPTER 19 THE ROLE OF DRUG METABOLISM AND PHARMACOKINETICS IN DRUG DISCOVERY: PAST, PRESENT AND FUTURE 359(23)
Mike Tarbit
19.1 Introduction
359(2)
19.2 The first principle: potency versus efficacy
361(2)
19.3 Which are the key kinetic parameters to measure?
363(1)
19.4 Assessment of absorption and systemic availability
363(4)
19.5 Cell-based models of absorption
367(1)
19.6 The importance of clearance
368(3)
19.7 Distribution and protein binding
371(1)
19.8 Half-life and duration of action
372(1)
19.9 Modifying structures to block metabolism
373(2)
19.10 What do we do about inhibitors and inducers?
375(1)
19.11 What does the ideal drug look like?
376(1)
19.12 The future
377(2)
19.13 Summary
379(1)
19.14 References
379(3)
Index 382


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