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Basic Pharmacokinetics and Pharmacodynamics
An Integrated Textbook and Computer Simulations
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Main description:

Updated with new chapters and topics, this book provides a comprehensive description of all essential topics in contemporary pharmacokinetics and pharmacodynamics. It also features interactive computer simulations for students to experiment and observe PK/PD models in action. Presents the essentials of pharmacokinetics and pharmacodynamics in a clear and progressive manner Helps students better appreciate important concepts and gain a greater understanding of the mechanism of action of drugs by reinforcing practical applications in both the book and the computer modules Features interactive computer simulations, available online through a companion website at: http://www.uri.edu/pharmacy/faculty/rosenbaum/basicmodels.html Adds new chapters on physiologically based pharmacokinetic models, predicting drug-drug interactions, and pharmacogenetics while also strengthening original chapters to better prepare students for more advanced applications Reviews of the 1st edition: This is an ideal textbook for those starting out and also for use as a reference book ."
(International Society for the Study of Xenobiotics) and 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 . (British Toxicology Society Newsletter)


Contents:

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


PRODUCT DETAILS

ISBN-13: 9781119143185
Publisher: John Wiley & Sons Ltd (John Wiley & Sons Inc)
Publication date: December, 2016
Pages: 608

Subcategories: Diseases and Disorders, Genetics, Pharmacology