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Principles of Clinical Pharmacology
von: Arthur J. Atkinson, Jr., Darrell R. Abernethy, Charles E. Daniels, Robert Dedrick, Sanford P. Markey
Elsevier Reference Monographs, 2011
ISBN: 9780080466422 , 568 Seiten
2. Auflage
Format: PDF, ePUB, OL
Kopierschutz: DRM
Preis: 96,95 EUR
Front cover
1
Title page
4
Copyright page
5
Table of contents
6
Preface to the First Edition
16
Preface to the Second Edition
16
Contributors
18
CHAPTER 1. Introduction to Clinical Pharmacology
22
BACKGROUND
22
PHARMACOKINETICS
25
PART I: PHARMACOKINETICS
30
CHAPTER 2. Clinical Pharmacokinetics
32
THE TARGET CONCENTRATION STRATEGY
32
CONCEPTS UNDERLYING CLINICAL PHARMACOKINETICS
34
MATHEMATICAL BASIS OF CLINICAL PHARMACOKINETICS
39
CHAPTER 3. Compartmental Analysis of Drug Distribution
46
PHYSIOLOGICAL SIGNIFICANCE OF DRUG DISTRIBUTION VOLUMES
46
PHYSIOLOGICAL BASIS OF MULTICOMPARTMENTAL MODELS OF DRUG DISTRIBUTION
48
CLINICAL CONSEQUENCES OF DIFFERENT DRUG DISTRIBUTION PATTERNS
51
ANALYSIS OF EXPERIMENTAL DATA
52
CHAPTER 4. Drug Absorption and Bioavailability
58
DRUG ABSORPTION
58
BIOAVAILABILITY
61
KINETICS OF DRUG ABSORPTION AFTER ORAL ADMINISTRATION
65
CHAPTER 5. Effects of Renal Disease on Pharmacokinetics
72
EFFECTS OF RENAL DISEASE ON DRUG ELIMINATION
73
EFFECTS OF RENAL DISEASE ON DRUG DISTRIBUTION
76
EFFECTS OF RENAL DISEASE ON DRUG ABSORPTION
77
CHAPTER 6. Pharmacokinetics in Patients Requiring Renal Replacement Therapy
80
KINETICS OF INTERMITTENT HEMODIALYSIS
80
KINETICS OF CONTINUOUS RENAL REPLACEMENT THERAPY
86
CLINICAL CONSIDERATIONS
88
CHAPTER 7. Effect of Liver Disease on Pharmacokinetics
94
HEPATIC ELIMINATION OF DRUGS
94
EFFECTS OF LIVER DISEASE ON PHARMACOKINETICS
97
USE OF THERAPEUTIC DRUGS IN PATIENTS WITH LIVER DISEASE
101
CHAPTER 8. Noncompartmental versus Compartmental Approaches to Pharmacokinetic Analysis
110
INTRODUCTION
110
KINETICS, PHARMACOKINETICS, AND PHARMACOKINETIC PARAMETERS
111
NONCOMPARTMENTAL ANALYSIS
113
COMPARTMENTAL ANALYSIS
118
NONCOMPARTMENTAL VERSUS COMPARTMENTAL MODELS
123
CONCLUSION
126
CHAPTER 9. Distributed Models of Drug Kinetics
128
INTRODUCTION
128
CENTRAL ISSUES
128
DRUG MODALITY I: DELIVERY ACROSS A PLANAR – TISSUE INTERFACE
129
DRUG MODALITY II: DELIVERY FROM A POINT SOURCE — DIRECT INTERSTITIAL INFUSION
138
SUMMARY
147
CHAPTER 10. Population Pharmacokinetics
150
INTRODUCTION
150
ANALYSIS OF PHARMACOKINETIC DATA
150
POPULATION PHARMACOKINETICS
151
MODEL APPLICATIONS
155
CONCLUSIONS
159
PART II: DRUG METABOLISM AND TRANSPORT
162
CHAPTER 11. Pathways of Drug Metabolism
164
INTRODUCTION
164
PHASE I BIOTRANSFORMATIONS
167
PHASE II BIOTRANSFORMATIONS (CONJUGATIONS)
177
ADDITIONAL EFFECTS ON DRUG METABOLISM
180
CHAPTER 12. Methods of Analysis of Drugs and Drug Metabolites
184
INTRODUCTION
184
CHOICE OF ANALYTICAL METHODOLOGY
184
CHROMATOGRAPHIC SEPARATIONS
185
ABSORPTION AND EMISSION SPECTROSCOPY
186
IMMUNOAFFINITY ASSAYS
187
MASS SPECTROMETRY
188
EXAMPLES OF CURRENT ASSAY METHODS
191
CHAPTER 13. Clinical Pharmacogenetics
200
INTRODUCTION
200
HIERARCHY OF PHARMACOGENETIC INFORMATION
201
IDENTIFICATION AND SELECTION OF OUTLIERS IN A POPULATION
202
EXAMPLES OF IMPORTANT GENETIC POLYMORPHISMS
204
CONCLUSIONS AND FUTURE DIRECTIONS
212
CHAPTER 14. Equilibrative and Concentrative Transport Mechanisms
218
INTRODUCTION
218
MECHANISMS OF TRANSPORT ACROSS BIOLOGICAL MEMBRANES
218
DESCRIPTION OF SELECTED MEMBRANE PROTEIN TRANSPORTERS
225
ROLE OF TRANSPORTERS IN PHARMACOKINETICS AND DRUG ACTION
230
PHARMACOGENETICS AND PHARMACOGENOMICS OF TRANSPORTERS
236
FUTURE DIRECTIONS
241
CHAPTER 15. Drug Interactions
250
INTRODUCTION
250
MECHANISMS OF DRUG INTERACTIONS
251
PREDICTION AND CLINICAL MANAGEMENT OF DRUG INTERACTIONS
263
CHAPTER 16. Biochemical Mechanisms of Drug Toxicity
270
INTRODUCTION
270
DRUG-INDUCED LIVER TOXICITY
274
MECHANISMS OF OTHER DRUG TOXICITIES
280
PART III: ASSESSMENT OF DRUG EFFECTS
294
CHAPTER 17. Physiological and Laboratory Markers of Drug Effect
296
BIOLOGICAL MARKERS OF DRUG EFFECT
296
IDENTIFICATION AND EVALUATION OF BIOMARKERS
298
USES OF BIOMARKERS AND SURROGATE ENDPOINTS
300
FUTURE DEVELOPMENT OF BIOMARKERS
304
CHAPTER 18. Dose-Effect and Concentration-Effect Analysis
310
BACKGROUND
310
DRUG–RECEPTOR INTERACTIONS
311
GRADED DOSE-EFFECT RELATIONSHIP
313
QUANTAL DOSE-EFFECT RELATIONSHIP
316
PHARMACODYNAMIC MODELS
319
CONCLUSION
320
CHAPTER 19. Time Course of Drug Response
322
PHARMACOKINETICS AND DELAYED PHARMACOLOGIC EFFECTS
323
PHYSIOKINETICS — TIME COURSE OF EFFECTS DUE TO PHYSIOLOGICAL TURNOVER PROCESSES
328
THERAPEUTIC RESPONSE, CUMULATIVE DRUG EFFECTS, AND SCHEDULE DEPENDENCE
329
CHAPTER 20. Disease Progress Models
334
CLINICAL PHARMACOLOGY AND DISEASE PROGRESS
334
DISEASE PROGRESS MODELS
334
CONCLUSION
341
PART IV: OPTIMIZING AND EVALUATING PATIENT THERAPHY
344
CHAPTER 21. Pharmacological Differences between Men and Women
346
PHARMACOKINETICS
346
PHARMACODYNAMICS
352
SUMMARY
355
CHAPTER 22. Drug Therapy in Pregnant and Nursing Women
360
PREGNANCY PHYSIOLOGY AND ITS EFFECTS ON PHARMACOKINETICS
361
PHARMACOKINETIC STUDIES DURING PREGNANCY
365
PLACENTAL TRANSFER OF DRUGS
369
TERATOGENESIS
370
DRUG THERAPY IN NURSING MOTHERS
373
CHAPTER 23. Drug Therapy in Neonates and Pediatric Patients
380
BACKGROUND
380
ONTOGENY AND PHARMACOLOGY
383
THERAPEUTIC IMPLICATIONS OF GROWTH AND DEVELOPMENT
387
CONCLUSIONS
392
CHAPTER 24. Drug Therapy in the Elderly
396
INTRODUCTION
396
PATHOPHYSIOLOGY OF AGING
396
AGE-RELATED CHANGES IN PHARMACOKINETICS
398
AGE-RELATED CHANGES IN EFFECTOR SYSTEM FUNCTION
400
DRUG GROUPS FOR WHICH AGE CONFERS INCREASED RISK FOR TOXICITY
404
CONCLUSIONS
406
CHAPTER 25. Clinical Analysis of Adverse Drug Reactions
410
INTRODUCTION
410
CLASSIFICATION
411
CLINICAL DETECTION
412
ADR DETECTION IN CLINICAL TRIALS
419
INFORMATION SOURCES
420
CHAPTER 26. Quality Assessment of Drug Therapy
424
INTRODUCTION
424
ORGANIZATIONAL INFLUENCES ON MEDICATION USE QUALITY
427
SUMMARY
438
PART V: DRUG DISCOVERY AND DEVELOPMENT
442
CHAPTER 27. Portfolio and Project Planning and Management in the Drug Discovery, Development, and Review Process
444
INTRODUCTION
444
PORTFOLIO DESIGN, PLANNING, AND MANAGEMENT
445
PROJECT PLANNING AND MANAGEMENT
450
PROJECT PLANNING AND MANAGEMENT TOOLS
452
PROJECT TEAM MANAGEMENT AND DECISION-MAKING
455
CHAPTER 28. Drug Discovery
460
INTRODUCTION
460
DEFINITION OF DRUG TARGETS
460
GENERATING DIVERSITY
464
DEFINITION OF LEAD STRUCTURES
465
QUALIFYING LEADS FOR TRANSITION TO EARLY TRIALS
466
CHAPTER 29. Preclinical Drug Development
470
INTRODUCTION
470
COMPONENTS OF PRECLINICAL DRUG DEVELOPMENT
471
DRUG DEVELOPMENT PROGRAMS AT THE NCI
477
THE CHALLENGE — MOLECULARLY TARGETED THERAPIES AND NEW PARADIGMS FOR CLINICAL TRIALS
480
CHAPTER 30. Animal Scale-Up
484
INTRODUCTION
484
ALLOMETRY
484
PHYSIOLOGICAL PHARMACOKINETICS
488
IN VITRO-IN VIVO CORRELATION OF HEPATIC METABOLISM
490
CHAPTER 31. Phase I Clinical Studies
494
INTRODUCTION
494
DISEASE-SPECIFIC CONSIDERATIONS
494
STARTING DOSE AND DOSE ESCALATION
495
BEYOND TOXICITY
498
CHAPTER 32. Development of Biotechnology Products and Large Molecules
500
INTRODUCTION
500
PHARMACOKINETIC CHARACTERISTICS OF MACROMOLECULES
504
PHARMACODYNAMICS
515
CHAPTER 33. Design of Clinical Development Programs
522
INTRODUCTION
522
PHASES, SIZE, AND SCOPE OF CLINICAL DEVELOPMENT PROGRAMS
522
GOAL AND OBJECTIVES OF CLINICAL DRUG DEVELOPMENT
526
CRITICAL DRUG DEVELOPMENT PARADIGMS
528
CRITICAL CLINICAL DRUG DEVELOPMENT DECISION POINTS
530
LEARNING CONTEMPORARY CLINICAL DRUG DEVELOPMENT
535
CHAPTER 34. Role of the FDA in Guiding Drug Development
540
WHY DOES THE FDA GET INVOLVED IN DRUG DEVELOPMENT?
541
WHEN DOES THE FDA GET INVOLVED IN DRUG DEVELOPMENT?
541
HOW DOES THE FDA GUIDE DRUG DEVELOPMENT?
542
WHAT ARE FDA GUIDANCES?
544
APPENDIX I. Abbreviated Tables of Laplace Transforms
548
APPENDIX II. Answers to Study Problems
550
Index
558
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