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Basic Pharmacokinetics and Pharmacodynamics: An Integrated Textbook and Computer Simulations

Editat de Sara E. Rosenbaum
Notă GoodReads:
en Limba Engleză Carte Paperback – 17 Jan 2017
Reviews of the First Edition:
 
“I could recommend Rosenbaum’s book for pharmacology students because it is written from a perspective of drug action . . . Overall, this is a well–written introduction to PK/PD that may fill a small niche in a well–served market. “  (British Toxicology Society Newsletter, 1 June 2012)
"In summary, I believe that this book is successful in what it sets out to do. For those readers who are interested in getting to grips with the basics of the time course of onset, offset and extent of drug effects then this is the book for you. I am certainly recommending this book for my graduate students." (British Journal of Clinical Pharmacology, 2011) Scientists working in pharmacokinetics and pharmacodynamics (PK and PD) study the behavior of drugs in the body. This includes how drugs are absorbed into the body, where they go, what they do, and how the body gets rid of them. Models can be applied to help understand these processes. The combined subject of PK/PD is an important component of the education of health professionals and research scientists involved with drugs.
Updated with new chapters and topics, the new edition of Basic Pharmacokinetics and Pharmacodynamics; presents the essentials of PK / PD in a clear and coordinated manner. Maintaining its clear and straightforward presentation, the text enables you to understand the dose–response relationship and dosing regimen design.
Your understanding of the material will be enhanced by guided computer exercises available on a companion website, which makes the book ideal for self–study. Simulations will allow you to visualize drug behaviour, experiment with different dosing regimens, and observe the influence of patient characteristics and model parameters.
The second edition updates and strengthens existing chapters and adds new topics to address newer applications of pharmacokinetics in clinical practice and drug development, including physiologically based pharmacokinetic modeling and the prediction of drug–drug interactions.
Because Basic Pharmacokinetics and Pharmacodynamics, 2nd Edition is an introductory textbook, the material is presented as simply as possible. As a result, you′ll find it easy to gain an understanding of all the core principles, apply them to understand drug dosages, drug–drug interactions, and to evaluate the literature on clinical pharmacokinetics and pharmacodynamics.
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Specificații

ISBN-13: 9781119143154
ISBN-10: 1119143152
Pagini: 576
Dimensiuni: 179 x 254 x 26 mm
Greutate: 1.18 kg
Ediția: 2nd Edition
Editura: Wiley
Locul publicării: Hoboken, United States

Public țintă

Undergrad and grad courses on pharmacokinetics and –dynamics (PK / PD), students in pharmacy, medical, pharmaceutical science, pharmacology

Pharmaceutical scientists and researchers in academia and industry

Textul de pe ultima copertă

Reviews of the First Edition:
 
“I could recommend Rosenbaum’s book for pharmacology students because it is written from a perspective of drug action . . . Overall, this is a well–written introduction to PK/PD that may fill a small niche in a well–served market. “  (British Toxicology Society Newsletter, 1 June 2012)
"In summary, I believe that this book is successful in what it sets out to do. For those readers who are interested in getting to grips with the basics of the time course of onset, offset and extent of drug effects then this is the book for you. I am certainly recommending this book for my graduate students." (British Journal of Clinical Pharmacology, 2011) Scientists working in pharmacokinetics and pharmacodynamics (PK and PD) study the behavior of drugs in the body. This includes how drugs are absorbed into the body, where they go, what they do, and how the body gets rid of them. Models can be applied to help understand these processes. The combined subject of PK/PD is an important component of the education of health professionals and research scientists involved with drugs.
Updated with new chapters and topics, the new edition of Basic Pharmacokinetics and Pharmacodynamics; presents the essentials of PK / PD in a clear and coordinated manner. Maintaining its clear and straightforward presentation, the text enables you to understand the dose–response relationship and dosing regimen design.
Your understanding of the material will be enhanced by guided computer exercises available on a companion website, which makes the book ideal for self–study. Simulations will allow you to visualize drug behaviour, experiment with different dosing regimens, and observe the influence of patient characteristics and model parameters.
The second edition updates and strengthens existing chapters and adds new topics to address newer applications of pharmacokinetics in clinical practice and drug development, including physiologically based pharmacokinetic modeling and the prediction of drug–drug interactions.
Because Basic Pharmacokinetics and Pharmacodynamics, 2nd Edition is an introductory textbook, the material is presented as simply as possible. As a result, you′ll find it easy to gain an understanding of all the core principles, apply them to understand drug dosages, drug–drug interactions, and to evaluate the literature on clinical pharmacokinetics and pharmacodynamics.

Cuprins

Preface xix
Contributors xxi
1 Introduction to Pharmacokinetics and Pharmacodynamics 1
Sara E. Rosenbaum
1.1 Introduction: Drugs and Doses, 2
1.2 Introduction to Pharmacodynamics, 3
1.3 Introduction to Pharmacokinetics, 9
1.4 Dose–Response Relationships, 12
1.5 Therapeutic Range, 14
1.6 Summary, 18
Reference, 18
2 Passage of Drugs Through Membranes 19
Sara E. Rosenbaum
2.1 Introduction, 20
2.2 Structure and Properties of Membranes, 20
2.3 Passive Diffusion, 21
2.4 Carrier–Mediated Processes: Transport Proteins, 26
References, 33
3 Drug Administration and Drug Absorption 35
Steven C. Sutton
3.1 Introduction: Local and Systemic Drug Administration, 36
3.2 Routes of Drug Administration, 37
3.3 Overview of Oral Absorption, 41
3.4 Extent of Drug Absorption, 44
3.5 Determinants of the Fraction of the Dose Absorbed (F), 46
3.6 Factors Controlling the Rate of Drug Absorption, 61
3.7 Biopharmaceutics Classification System, 64
3.8 Food Effects, 65
Problems, 66
References, 67
4 Drug Distribution 71
Sara E. Rosenbaum
4.1 Introduction, 72
4.2 Extent of Drug Distribution, 72
4.3 Rate of Drug Distribution, 89
4.4 Distribution of Drugs to the Central Nervous System, 93
Problems, 96
References, 98
5 Drug Elimination and Clearance 99
Sara E. Rosenbaum
5.1 Introduction, 100
5.2 Clearance, 102
5.3 Renal Clearance, 108
5.4 Hepatic Elimination and Clearance, 119
Problems, 139
References, 142
6 Compartmental Models in Pharmacokinetics 145
Sara E. Rosenbaum
6.1 Introduction, 146
6.2 Expressions for Component Parts of the Dose–Plasma Concentration Relationship, 146
6.3 Putting Everything Together: Compartments and Models, 149
6.4 Examples of Complete Compartment Models, 152
6.5 Use of Compartmental Models to Study Metabolite Pharmacokinetics, 155
6.6 Selecting and Applying Models, 156
Problems, 157
Suggested Readings, 157
7 Pharmacokinetics of an Intravenous Bolus Injection in a One–Compartment Model 159
Sara E. Rosenbaum
7.1 Introduction, 160
7.2 One–Compartment Model, 160
7.3 Pharmacokinetic Equations, 162
7.4 Simulation Exercise, 163
7.5 Application of the Model, 165
7.6 Determination of Pharmacokinetic Parameters Experimentally, 168
7.7 Pharmacokinetic Analysis in Clinical Practice, 173
Problems, 174
Suggested Reading, 176
8 Pharmacokinetics of an Intravenous Bolus Injection in a Two–Compartment Model 177
Sara E. Rosenbaum
8.1 Introduction, 178
8.2 Tissue and Compartmental Distribution of a Drug, 179
8.3 Basic Equation, 181
8.4 Relationship Between Macro and Micro Rate Constants, 183
8.5 Primary Pharmacokinetic Parameters, 183
8.6 Simulation Exercise, 188
8.7 Determination of the Pharmacokinetic Parameters of the Two–Compartment Model, 191
8.8 Clinical Application of the Two–Compartment Model, 194
Problems, 197
Suggested Readings, 199
9 Pharmacokinetics of Extravascular Drug Administration 201
Dr. Steven C. Sutton
9.1 Introduction, 202
9.2 First–Order Absorption in a One–Compartment Model, 203
9.3 Modified Release and Gastric Retention Formulations, 214
9.4 Bioavailability, 215
9.5 In Vitro–In Vivo Correlation, 219
9.6 Simulation Exercise, 222
Problems, 223
References, 224
10 Introduction to Noncompartmental Analysis 225
Sara E. Rosenbaum
10.1 Introduction, 225
10.2 Mean Residence Time, 226
10.3 Determination of Other Important Pharmacokinetic Parameters, 229
10.4 Different Routes of Administration, 231
10.5 Application of Noncompartmental Analysis to Clinical Studies, 232
Problems, 234
11 Pharmacokinetics of Intravenous Infusion in a One–Compartment Model 237
Sara E. Rosenbaum
11.1 Introduction, 238
11.2 Model and Equations, 239
11.3 Steady–State Plasma Concentration, 242
11.4 Loading Dose, 246
11.5 Termination of Infusion, 248
11.6 Individualization of Dosing Regimens, 249
Problems, 252
12 Multiple Intravenous Bolus Injections in the One–Compartment Model 255
Sara E. Rosenbaum
12.1 Introduction, 256
12.2 Terms and Symbols Used in Multiple–Dosing Equations, 257
12.3 Monoexponential Decay During a Dosing Interval, 259
12.4 Basic Pharmacokinetic Equations for Multiple Doses, 260
12.5 Steady State, 262
12.6 Basic Formula Revisited, 270
12.7 Pharmacokinetic–Guided Dosing Regimen Design, 270
12.8 Simulation Exercise, 276
Problems, 277
Reference, 278
13 Multiple Intermittent Infusions 279
Sara E. Rosenbaum
13.1 Introduction, 279
13.2 Steady–State Equations for Multiple Intermittent Infusions, 281
13.3 Monoexponential Decay During a Dosing Interval: Determination of Peaks, Troughs, and Elimination Half–Life, 284
13.4 Determination of the Volume of Distribution, 286
13.5 Individualization of Dosing Regimens, 289
13.6 Simulation, 289
Problems, 290
14 Multiple Oral Doses 293
Sara E. Rosenbaum
14.1 Introduction, 293
14.2 Steady–State Equations, 294
14.3 Equations Used Clinically to Individualize Oral Doses, 298
14.4 Simulation Exercise, 300
References, 301
15 Nonlinear Pharmacokinetics 303
Sara E. Rosenbaum
15.1 Linear Pharmacokinetics, 304
15.2 Nonlinear Processes in Absorption, Distribution, Metabolism, and Elimination, 306
15.3 Pharmacokinetics of Capacity–Limited Metabolism, 307
15.4 Phenytoin, 310
Problems, 321
References, 322
16 Introduction to Pharmacogenetics 323
Dr. Daniel Brazeau
16.1 Introduction, 324
16.2 Genetics Primer, 324
16.3 Pharmacogenetics, 328
16.4 Genetics and Pharmacodynamics, 334
16.5 Summary, 335
Reference, 335
Suggested Readings, 335
17 Models Used to Predict Drug–Drug Interactions for Orally Administered Drugs 337
Sara E. Rosenbaum
17.1 Introduction, 338
17.2 Mathematical Models for Inhibitors and Inducers of Drug Metabolism Based on In Vitro Data, 340
17.3 Surrogate In Vivo Values for the Unbound Concentration of the Perpetrator at the Site of Action, 345
17.4 Models Used to Predict DDIs In Vivo, 347
17.5 Predictive Models for Transporter–Based DDIs, 359
17.6 Application of Physiologically Based Pharmacokinetic Models to DDI Prediction: The Dynamic Approach, 362
17.7 Conclusion, 362
Problems, 363
References, 364
18 Introduction to Physiologically Based Pharmacokinetic Modeling 367
Sara E. Rosenbaum
18.1 Introduction, 368
18.2 Components of PBPK Models, 369
18.3 Equations for PBPK Models, 369
18.4 Building a PBPK Model, 373
18.5 Simulations, 377
18.6 Estimation of Human Drug–Specific Parameters, 378
18.7 More Detailed PBPK Models, 381
18.8 Application of PBPK Models, 387
References, 388
19 Introduction to Pharmacodynamic Models and Integrated Pharmacokinetic–Pharmacodynamic Models 391
Drs. Diane Mould and Paul Hutson
19.1 Introduction, 392
19.2 Classic Pharmacodynamic Models Based on Receptor Theory, 393
19.3 Direct Effect Pharmacodynamic Models, 402
19.4 Integrated PK–PD Models: Intravenous Bolus Injection in the One–Compartment Mode and the Sigmoidal Emax Model, 406
19.5 Pharmacodynamic Drug–Drug Interactions, 410
Problems, 411
References, 412
20 Semimechanistic Pharmacokinetic–Pharmacodynamic Models 413
Drs. Diane Mould and Paul Hutson
20.1 Introduction, 414
20.2 Hysteresis and the Effect Compartment, 416
20.3 Physiological Turnover Models and Their Characteristics, 419
20.4 Indirect Effect Models, 422
20.5 Other Indirect Effect Models, 432
20.6 Models of Tolerance, 442
20.7 Irreversible Drug Effects, 450
20.8 Disease Progression Models, 452
Problems, 459
References, 465
Appendix A Review of Exponents and Logarithms 469
Sara E. Rosenbaum
A.1 Exponents, 469
A.2 Logarithms: Log and Ln, 470
A.3 Performing Calculations in the Logarithmic Domain, 471
A.4 Calculations Using Exponential Expressions and Logarithms, 472
A.5 Decay Function: e−kt, 474
A.6 Growth Function: 1 − e−kt, 475
A.7 Decay Function in Pharmacokinetics, 475
Problems, 476
Appendix B Rates of Processes 479
Sara E. Rosenbaum
B.1 Introduction, 479
B.2 Order of a Rate Process, 480
B.3 Zero–Order Processes, 480
B.4 First–Order Processes, 482
B.5 Comparison of Zero– and First–Order Processes, 484
B.6 Detailed Example of First–Order Decay in Pharmacokinetics, 484
B.7 Examples of the Application of First–Order Kinetics to Pharmacokinetics, 487
Appendix C Creation of Excel Worksheets for Pharmacokinetic Analysis 489
Sara E. Rosenbaum
C.1 Measurement of AUC and Clearance, 489
C.2 Analysis of Data from an Intravenous Bolus Injection in a One–Compartment Model, 494
C.3 Analysis of Data from an Intravenous Bolus Injection in a Two–Compartment Model, 496
C.4 Analysis of Oral Data in a One–Compartment Model, 498
C.5 Noncompartmental Analysis of Oral Data, 501
Appendix D Derivation of Equations for Multiple Intravenous Bolus Injections 505
Sara E. Rosenbaum
D.1 Assumptions, 505
D.2 Basic Equation for Plasma Concentration After Multiple Intravenous Bolus Injections, 505
D.3 Steady–State Equations, 508
Appendix E Enzyme Kinetics: Michaelis–Menten Equation and Models for Inhibitors and Inducers of Drug Metabolism 509
Sara E. Rosenbaum and Roberta S. King
E.1 Kinetics of Drug Metabolism: The Michaelis–Menten Model, 510
E.2 Effect of Perpetrators of DDI on Enzyme Kinetics and Intrinsic Clearance, 515
References, 526
Appendix F Summary of the Properties of the Fictitious Drugs Used in the Text 527
Sara E. Rosenbaum
Appendix G Computer Simulation Models 529
Sara E. Rosenbaum
Glossary of Terms 531
Index 537

Notă biografică

Sara E. Rosenbaum, PhD, is Professor of Biomedical and Pharmaceutical Sciences at the University of Rhode Island, where she teaches courses in pharmacokinetics and pharmacodynamics. Her research interests concentrate on the development and application of pharmacokinetic and pharmacodynamic models to better understand the drug dose–response relationship.