Introduction to Pharmacokinetics and Pharmacodynamics: The Quantitative Basis of Drug Therapy

Introduction to Pharmacokinetics and Pharmacodynamics: The Quantitative Basis of Drug Therapy......Page 1
Title Page......Page 3
Copyright......Page 4
Dedication......Page 5
About the Authors......Page 7
Preface......Page 9
Contents......Page 11
THE CLINICAL SETTING......Page 13
ORGANIZATION OF THE BOOK......Page 22
SECTION I: Basic Considerations......Page 25
OBJECTIVES......Page 27
SYSTEMIC EXPOSURE......Page 28
PERIOD OF OBSERVATION......Page 29
ANATOMIC AND PHYSIOLOGIC CONSIDERATIONS......Page 30
CHEMICAL PURITY AND ANALYTIC SPECIFICITY......Page 31
DEFINITIONS......Page 32
BASIC MODEL FOR DRUG ABSORPTION AND DISPOSITION......Page 35
STUDY PROBLEMS......Page 37
OBJECTIVES......Page 39
CLASSIFICATION OF RESPONSE......Page 40
ASSESSMENT OF DRUG EFFECT......Page 42
RELATING CONCENTRATION TO RESPONSE......Page 45
EXPOSURE–RESPONSE RELATIONSHIPS......Page 49
SUMMARY......Page 50
STUDY PROBLEMS......Page 51
SECTION II: Exposure and Response After a Single Dose......Page 55
OBJECTIVES......Page 57
MEMBRANES......Page 58
TRANSPORT PROCESSES......Page 59
BLOOD FLOW VERSUS PERMEABILITY......Page 68
REVERSIBLE NATURE OF TRANSPORT......Page 71
SUMMARY......Page 72
STUDY PROBLEMS......Page 73
OBJECTIVES......Page 75
APPRECIATION OF KINETIC CONCEPTS......Page 76
A CASE STUDY......Page 83
PATHWAYS OF ELIMINATION......Page 88
HALF-LIFE, CLEARANCE, AND DISTRIBUTION......Page 90
WHY DOES DISTRIBUTION VARY SO WIDELY AMONG DRUGS?......Page 91
WHY DOES CLEARANCE VARY SO WIDELY AMONG DRUGS?......Page 102
SUMMARY......Page 112
STUDY PROBLEMS......Page 113
OBJECTIVES......Page 117
KINETICS OF ABSORPTION......Page 119
EXPOSURE-TIME AND EXPOSURE–DOSE RELATIONSHIPS......Page 120
CHANGES IN DOSE OR ABSORPTION KINETICS......Page 123
ABSORPTION FROM SOLUTION......Page 126
ABSORPTION FROM SOLID DOSAGE FORMS......Page 137
ASSESSMENT OF PRODUCT PERFORMANCE......Page 142
SUMMARY......Page 144
STUDY PROBLEMS......Page 146
OBJECTIVES......Page 149
TIME DELAYS BETWEEN CONCENTRATION AND RESPONSE......Page 150
DECLINE OF RESPONSE WITH TIME......Page 156
ONSET AND DURATION OF RESPONSE......Page 159
SUMMARY......Page 162
STUDY PROBLEMS......Page 163
SECTION III: Therapeutic Regimens......Page 167
DOSAGE REGIMENS......Page 169
THERAPEUTIC WINDOW......Page 171
THERAPEUTIC CORRELATES......Page 175
ADDITIONAL CONSIDERATIONS......Page 176
KEY TERM REVIEW......Page 178
STUDY PROBLEMS......Page 179
OBJECTIVES......Page 181
EXPOSURE–TIME RELATIONSHIPS......Page 184
SHORT-TERM INFUSIONS......Page 192
CONSEQUENCE OF SLOW TISSUE DISTRIBUTION......Page 193
PHARMACODYNAMIC CONSIDERATIONS......Page 194
SUMMARY......Page 195
STUDY PROBLEMS......Page 196
OBJECTIVES......Page 201
PRINCIPLES OF DRUG ACCUMULATION......Page 202
RELATIONSHIP BETWEEN INITIAL AND MAINTENANCE DOSES......Page 208
MAINTENANCE OF DRUG IN THE THERAPEUTIC RANGE......Page 210
ADDITIONAL CONSIDERATIONS......Page 215
MODIFIED-RELEASE PRODUCTS......Page 217
PHARMACODYNAMIC CONSIDERATIONS......Page 218
SUMMARY......Page 224
STUDY PROBLEMS......Page 225
SECTION IV: Individualization......Page 229
OBJECTIVES......Page 231
EXPRESSIONS OF INDIVIDUAL DIFFERENCES......Page 232
WHY PEOPLE DIFFER......Page 236
SUMMARY......Page 256
STUDY PROBLEMS......Page 257
OBJECTIVES......Page 261
ANTICIPATING SOURCES OF VARIABILITY......Page 262
INITIATING THERAPY......Page 268
MANAGING THERAPY......Page 270
DISCONTINUING THERAPY......Page 276
SUMMARY......Page 277
STUDY PROBLEMS......Page 278
Definitions of Symbols......Page 279
Nonproprietary and Brand Names of Drugs in Text and Illustrations......Page 283
APPENDIX A: Assessment of AUC......Page 287
STUDY PROBLEM......Page 288
APPENDIX B: Ionization and the pH Partition Hypothesis......Page 291
STUDY PROBLEMS......Page 293
DRUG ACCUMULATION......Page 295
STEADY STATE......Page 296
STUDY PROBLEMS......Page 297
CHAPTER 2......Page 299
CHAPTER 3......Page 301
CHAPTER 4......Page 303
CHAPTER 5......Page 305
CHAPTER 6......Page 309
CHAPTER 7......Page 311
CHAPTER 8......Page 314
CHAPTER 9......Page 315
CHAPTER 10......Page 318
CHAPTER 11......Page 322
CHAPTER 12......Page 325
APPENDIX B......Page 327
APPENDIX C......Page 328
Index......Page 329