A Handbook of Bioanalysis and Drug Metabolism

Front Cover
Gary Evans
CRC Press, Mar 29, 2004 - Medical - 408 pages
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 the field without a text/reference that is both instructional and practical in the industrial setting – until now.

A Handbook of Bioanalysis and Drug Metabolismis a stimulating new text that examines the techniques, methodology, and theory of bioanalysis, pharmacokinetics, and metabolism from the perspective of scientists with extensive professional experience in drug discovery and development. These three areas of research help drug developers to optimize the active component within potential drugs thereby increasing their effectiveness, and to provide safety and efficacy information required by regulators when granting a drug license. Professionals with extensive experience in drug discovery and development as well as specialized knowledge of the individual topics contributed to each chapter to create a current and well-credentialed text. It covers topics such as high performance liquid chromatography, protein binding, pharmacokinetics and drug–drug interactions. The unique industrial perspective helps to reinforce theory and develop valuable analytical and interpreting skills.

This text is an invaluable guide to students in courses such as pharmaceutical science, pharmacology, chemistry, physiology and toxicology, as well as professionals in the biotechnology industry.

 

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Contents

Introduction Gary Evans
1
12 The role of BPDM in drug discovery and drug development
2
The importance of the physicochemical properties of drugs to drug metabolism David Spalding
8
22 The physicochemical nature of drug molecules
9
23 The structure of the cell membrane and its implications for drug disposition
10
24 Drug partitioning across membranes
11
25 The ionisation of drugs
13
26 The pH environment of the body and how it affects drug absorption and distribution
17
1O8 References
175
Isotope drug studies in man Graeme Young John Ayrton and Tony Pateman
176
1 1 2 Which isotope?
181
1 1 4 Accelerator mass spectrometry
186
1 1 5 Future of AMS
189
116 Stable isotope studies
190
Whole body autoradiography Lee Grossman Kenneth Brouwer and Jeanne Jarrett
191
1 22 Historical background
192

27 The importance of the physicochemical properties of drugs to their metabolism and excretion
20
28 Chirality and its effects on drug absorption metabolism and excretion
24
29 The importance of physicochemicalproperties to the analysis of drugs
27
21 O Summary
29
Sample preparation Bob Biddlecombe and Glenn Smith
32
33 Instrumentation
35
34 Bioanalytical automation strategy
36
35 future development
42
36 References
43
Highperformance liquid chromatography in pharmaceutical bioanalysis David N Mallett
45
42 A brief look at the theory of chromatographic separation in HPLC
46
43 The basic equipment comprising a modern HPLC system
49
44 M odes of liquid chromatography
57
45 Highthroughput bioanalysis
64
46 Chiral HPLC
65
47 Future trends in HPLC
66
48 Bibliography
68
Mass spectrometry and quantitative bioanalysis Bob Biddlecombe Sheryl Callejas and Gary Evans
69
52 The instruments
70
54 lonisation
73
55 Mass analysers
75
56 Use of MS in quantitative LCMS
76
57 Developing an LCMS assay method
77
58 Bibliography
89
Immunoassay in pharmacokinetic and pharmacodynamic bioanalysis Richard Nicholl Paul Linacre and Bill Jenner
90
62 The role of immunoassay in drug discovery and development
91
63 Principles of immunoassay
92
64 Assay development
95
66 Selection and production of label
96
67 Assay development and optimisation
98
68 Assay validation
99
69 Immunoassays developed inhouse
100
61O Commercial kit immunoassay
102
611 Data handling
103
613 Biomarkers
105
determination of COX2 selectivity in human blood
107
615 Biological drugs
108
61 6 References
112
Preclinical pharmacokinetics Sheila Schwartz and Tony Pateman
113
72 Pharmacokinetic parameters
115
74 Calculation of pharmacokinetic parameters
116
75 Parameter derivations
120
76 Study design and data handling in preclinical drug development
125
77 Application of PK in drug discovery
127
78 Interspecies scaling
129
79 References
131
Pharmacokineticl pharmacodynamic modelling in preclinical drug discovery Tony Pateman
132
82 Advantages of incorporating PKlPD modelling in the drug discovery process
133
83 PKlPD in the drug discovery process
134
84 Principles of PKlPD modelling
136
85 Summary
140
86 References
141
Toxicokinetics Sheila Schwartz
142
92 Study design
143
93 PK parameters for toxicokinetic evaluation
146
94 Reporting
149
95 Application of toxicokinetic data
150
96 Toxicokinetictoxicodynamic relationships
151
97 Dose and timedependencies
152
98 References
155
Protein binding in plasma a case history of a highly proteinbound drug Robert J Barnaby and Marco Bottacini
156
1O2 The protein binding equilibrium
157
1O4 Principal plasma binding proteins
158
1O5 The importance of protein binding in drug development
162
a brief review of the more popular techniques including advantages and disadvantages
166
a case history of a highly bound drug
168
1 24 Study design
193
1 25 Obtaining whole body sections
194
1 26 Imaging
195
1 27 Quantitative whole body autoradiography
196
1 28 Applications of quantitative whole body autoradiography
197
1 29 References
206
1 3 Phase I metabolism Peter Eddershaw and Maurice Dickins
208
1 32 Cytochrome P450s
209
1 33 Monoamine oxidases MAO
215
1 34 Flavin monooxygenases FMO
216
1 35 Alcohol dehydrogenases ADH and aldehyde dehydrogenases ALDH
218
1 37 Conclusions
221
14 Phase II enzymes Gary Manchee Maurice Dickins and Elizabeth Pickup
222
1 42 Phase II enzyme reactions
223
1 43 Nomenclature of phase II enzymes
232
1 44 Phase II enzymes and drug development
236
1 45 Summary
241
146 References
242
15 In vitro techniques for investigating drug metabolism Graham Somers Peter Mutch and Amanda Woodrooffe
244
1 52 Preparation of liver subcellular fractions and bepatocytes
247
1 53 Use of subcellular fractions hepatocytes and liver slices to study drug metabolism
254
1 54 In vitroin vivo correlations
256
1 55 Advantages and disadvantages of the in vitro systems used to study drug metabolism
258
1 56 The study of drug interactions using in vitro systems
261
1 57 References
266
Drugdrug interactions an in vitro approach DM Cross and MK Bayliss
269
1 62 Clinical background
270
1 64 The mechanism behind drugdrug interactions
271
1 65 Drugmetabolising enzymes
272
1 66 Drug transport systems
273
1 67 Plasma protein binding
274
1 68 Drug concentration effects
275
1 61 O Induction of drugmetabolising enzymes and its effect
280
1611 In vitro approaches to investigating drug interaction
281
1612 A regulatory perspective
286
1614 Overview
289
1 61 5 References
290
Identification of drug metabolites in biological fluids using qualitative spectroscopic and chromatographic techniques GJ Dear and IM Ismail
292
172 Mass spectrometry
293
173 Sample preparation
294
174 Phase I
295
175 Phase U
301
176 NMR spectroscopy
310
177 Characterisation of metabolites by H NMR
314
178 NMR metabolite profiling
322
Molecular biology Steve Hood
325
183 Which enzyme?
329
185 Induction or suppression?
341
186 Population genetics and polymorphisms
349
187 References
352
188 Bibliography
358
The role of drug metabolism and pharmacokinetics in drug discovery past present and future Mike Tarbit
359
potency versus efficacy
361
193 Which are the key kinetic parameters to measure?
363
195 Cellbased models of absorption
367
196 The importance of clearance
368
197 Distribution and protein binding
371
198 Halflife and duration of action
372
199 Modifying structures to block metabolism
373
191 O What do we do about inhibitors and inducers?
375
1911 What does the ideal drug look like?
376
191 2 The future
377
1913 Summary
379
Index
382
Copyright

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About the author (2004)

Gary Evans, author of "The National Interest: A Chronicle of the National Film Board of Canada from 1949 to 1989" (1991), has published extensively on the history of media and communications. A former student of John Grierson, Evans completed his degree in history at McGill and currently teaches at the University of Ottawa. Since 1975 he has also worked as a consultant and writer for the NFB.

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