{"product_id":"basic-pharmacokinetics-and-pharmacodynamics-an-integrated-textbook-and-computer-simulations-paperback-softback-9781119143154","title":"Basic Pharmacokinetics and Pharmacodynamics; An Integrated Textbook and Computer Simulations (Paperback \/ softback) 9781119143154","description":"\u003cfont face=\"Georgia\"\u003e\r\n\u003cp\u003e\u003cfont size=\"6\"\u003eBasic Pharmacokinetics and Pharmacodynamics\u003c\/font\u003e\u003cbr\u003e\r\n\u003cfont size=\"5\"\u003eAn Integrated Textbook and Computer Simulations\u003c\/font\u003e\u003c\/p\u003e\r\n\r\n\r\n\r\n\r\n\u003cp\u003e\u003cfont size=\"4\"\u003eSara E. Rosenbaum (Edited by), SE Rosenbaum (Author)\u003c\/font\u003e\u003c\/p\u003e\r\n\r\n\u003cp\u003e\u003cfont size=\"3\"\u003e9781119143154, Wiley\u003c\/font\u003e\u003c\/p\u003e\r\n\r\n\u003cp\u003e\u003cfont size=\"3\"\u003ePaperback \/ softback, published 17 January 2017\u003c\/font\u003e\u003c\/p\u003e\r\n\r\n\u003cp\u003e\u003cfont size=\"3\"\u003e576 pages\u003cbr\u003e24.9 x 17.5 x 3 cm, 1.021 kg\u003c\/font\u003e\u003c\/p\u003e\r\n\r\n\r\n\r\n\r\n\r\n\u003cp align=\"justify\"\u003e\u003cstrong\u003e\u003cfont size=\"3\"\u003eUpdated 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.\u003cbr\u003e\u003cbr\u003e•    Presents the essentials of pharmacokinetics and pharmacodynamics in a clear and progressive manner\u003cbr\u003e•    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\u003cbr\u003e•    Features interactive computer simulations, available online through a companion website at: https:\/\/web.uri.edu\/pharmacy\/research\/rosenbaum\/sims\/\u003cbr\u003e•    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\u003cbr\u003e•    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)\u003c\/font\u003e\u003c\/strong\u003e\u003c\/p\u003e\r\n\r\n\u003cp\u003e\u003cfont size=\"3\"\u003e\u003cp\u003ePreface xix\u003c\/p\u003e \u003cp\u003eContributors xxi\u003c\/p\u003e \u003cp\u003e\u003cb\u003e1 Introduction to Pharmacokinetics and Pharmacodynamics 1\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eSara E. Rosenbaum\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e1.1 Introduction: Drugs and Doses 2\u003c\/p\u003e \u003cp\u003e1.2 Introduction to Pharmacodynamics 3\u003c\/p\u003e \u003cp\u003e1.2.1 Drug Effects at the Site of Action 3\u003c\/p\u003e \u003cp\u003e1.2.2 Agonists, Antagonists, and Concentration–Response Relationships 6\u003c\/p\u003e \u003cp\u003e1.3 Introduction to Pharmacokinetics 9\u003c\/p\u003e \u003cp\u003e1.3.1 Plasma Concentration of Drugs 9\u003c\/p\u003e \u003cp\u003e1.3.2 Processes in Pharmacokinetics 11\u003c\/p\u003e \u003cp\u003e1.4 Dose–Response Relationships 12\u003c\/p\u003e \u003cp\u003e1.5 Therapeutic Range 14\u003c\/p\u003e \u003cp\u003e1.5.1 Determination of the Therapeutic Range 15\u003c\/p\u003e \u003cp\u003e1.6 Summary 18\u003c\/p\u003e \u003cp\u003eReference 18\u003c\/p\u003e \u003cp\u003e\u003cb\u003e2 Passage of Drugs Through Membranes 19\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eSara E. Rosenbaum\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e2.1 Introduction 20\u003c\/p\u003e \u003cp\u003e2.2 Structure and Properties of Membranes 20\u003c\/p\u003e \u003cp\u003e2.3 Passive Diffusion 21\u003c\/p\u003e \u003cp\u003e2.3.1 Transcellular Passive Diffusion 23\u003c\/p\u003e \u003cp\u003e2.3.2 Paracellular Passive Diffusion 25\u003c\/p\u003e \u003cp\u003e2.4 Carrier-Mediated Processes: Transport Proteins 26\u003c\/p\u003e \u003cp\u003e2.4.1 Uptake Transporters: SLC Superfamily 27\u003c\/p\u003e \u003cp\u003e2.4.2 Efflux Transporters: ABC Superfamily 29\u003c\/p\u003e \u003cp\u003e2.4.3 Characteristics of Transporter Systems 31\u003c\/p\u003e \u003cp\u003e2.4.4 Simulation Exercise 32\u003c\/p\u003e \u003cp\u003e2.4.5 Clinical Examples of Transporter Involvement in Drug Response 32\u003c\/p\u003e \u003cp\u003eReferences 33\u003c\/p\u003e \u003cp\u003e\u003cb\u003e3 Drug Administration and Drug Absorption 35\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eSteven C. Sutton\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e3.1 Introduction: Local and Systemic Drug Administration 36\u003c\/p\u003e \u003cp\u003e3.2 Routes of Drug Administration 37\u003c\/p\u003e \u003cp\u003e3.2.1 Common Routes of Local Drug Administration 37\u003c\/p\u003e \u003cp\u003e3.2.2 Common Routes of Systemic Drug Administration 38\u003c\/p\u003e \u003cp\u003e3.3 Overview of Oral Absorption 41\u003c\/p\u003e \u003cp\u003e3.3.1 Anatomy and Physiology of the Oral-Gastric-Intestinal Tract and Transit Time 41\u003c\/p\u003e \u003cp\u003e3.4 Extent of Drug Absorption 44\u003c\/p\u003e \u003cp\u003e3.4.1 Bioavailability Factor 44\u003c\/p\u003e \u003cp\u003e3.4.2 Individual Bioavailability Factors 45\u003c\/p\u003e \u003cp\u003e3.5 Determinants of the Fraction of the Dose Absorbed (\u003ci\u003eF\u003c\/i\u003e) 46\u003c\/p\u003e \u003cp\u003e3.5.1 Disintegration 46\u003c\/p\u003e \u003cp\u003e3.5.2 Dissolution 46\u003c\/p\u003e \u003cp\u003e3.5.3 Formulation Excipients 50\u003c\/p\u003e \u003cp\u003e3.5.4 Adverse Events within the Gastrointestinal Lumen 50\u003c\/p\u003e \u003cp\u003e3.5.5 Transcellular Passive Diffusion 53\u003c\/p\u003e \u003cp\u003e3.5.6 Particulate Uptake 53\u003c\/p\u003e \u003cp\u003e3.5.7 Paracellular Passive Diffusion 53\u003c\/p\u003e \u003cp\u003e3.5.8 Uptake and Efflux Transporters 54\u003c\/p\u003e \u003cp\u003e3.5.9 Presystemic Intestinal Metabolism or Extraction 58\u003c\/p\u003e \u003cp\u003e3.5.10 Presystemic Hepatic Metabolism or Extraction 60\u003c\/p\u003e \u003cp\u003e3.6 Factors Controlling the Rate of Drug Absorption 61\u003c\/p\u003e \u003cp\u003e3.6.1 Dissolution-Controlled Absorption 63\u003c\/p\u003e \u003cp\u003e3.6.2 Membrane Penetration-Controlled Absorption 63\u003c\/p\u003e \u003cp\u003e3.6.3 Overall Rate of Drug Absorption 63\u003c\/p\u003e \u003cp\u003e3.7 Biopharmaceutics Classification System 64\u003c\/p\u003e \u003cp\u003e3.7.1 Intestinal Reserve Length 64\u003c\/p\u003e \u003cp\u003e3.7.2 Biopharmaceutics Classification System (BCS) 64\u003c\/p\u003e \u003cp\u003e3.7.3 Biopharmaceutics Drug Disposition Classification System (BDDCS) 65\u003c\/p\u003e \u003cp\u003e3.8 Food Effects 65\u003c\/p\u003e \u003cp\u003eProblems 66\u003c\/p\u003e \u003cp\u003eReferences 67\u003c\/p\u003e \u003cp\u003e\u003cb\u003e4 Drug Distribution 71\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eSara E. Rosenbaum\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e4.1 Introduction 72\u003c\/p\u003e \u003cp\u003e4.2 Extent of Drug Distribution 72\u003c\/p\u003e \u003cp\u003e4.2.1 Distribution Volumes 74\u003c\/p\u003e \u003cp\u003e4.2.2 Tissue Binding Plasma Protein Binding and Partitioning: Concentrating Effects 75\u003c\/p\u003e \u003cp\u003e4.2.3 Assessment of the Extent of Drug Distribution: Apparent Volume of Distribution 76\u003c\/p\u003e \u003cp\u003e4.2.4 Plasma Protein Binding 82\u003c\/p\u003e \u003cp\u003e4.3 Rate of Drug Distribution 89\u003c\/p\u003e \u003cp\u003e4.3.1 Perfusion-Controlled Drug Distribution 90\u003c\/p\u003e \u003cp\u003e4.3.2 Diffusion or Permeability-Controlled Drug Distribution 93\u003c\/p\u003e \u003cp\u003e4.4 Distribution of Drugs to the Central Nervous System 93\u003c\/p\u003e \u003cp\u003eProblems 96\u003c\/p\u003e \u003cp\u003eReferences 98\u003c\/p\u003e \u003cp\u003e\u003cb\u003e5 Drug Elimination and Clearance 99\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eSara E. Rosenbaum\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e5.1 Introduction 100\u003c\/p\u003e \u003cp\u003e5.1.1 First-Order Elimination 101\u003c\/p\u003e \u003cp\u003e5.1.2 Determinants of the Elimination Rate Constant and the Half-Life 102\u003c\/p\u003e \u003cp\u003e5.2 Clearance 102\u003c\/p\u003e \u003cp\u003e5.2.1 Definition and Determinants of Clearance 102\u003c\/p\u003e \u003cp\u003e5.2.2 Total Clearance, Renal Clearance, and Hepatic Clearance 104\u003c\/p\u003e \u003cp\u003e5.2.3 Relationships among Clearance, Volume of Distribution, Elimination Rate Constant, and Half-Life 105\u003c\/p\u003e \u003cp\u003e5.2.4 Primary and Secondary Parameters 106\u003c\/p\u003e \u003cp\u003e5.2.5 Measurement of Total Body Clearance 106\u003c\/p\u003e \u003cp\u003e5.3 Renal Clearance 108\u003c\/p\u003e \u003cp\u003e5.3.1 Glomerular Filtration 109\u003c\/p\u003e \u003cp\u003e5.3.2 Tubular Secretion 110\u003c\/p\u003e \u003cp\u003e5.3.3 Tubular Reabsorption 113\u003c\/p\u003e \u003cp\u003e5.3.4 Putting Meaning into the Value of Renal Clearance 114\u003c\/p\u003e \u003cp\u003e5.3.5 Measurement of Renal Clearance 115\u003c\/p\u003e \u003cp\u003e5.3.6 Fraction of the Dose Excreted Unchanged 118\u003c\/p\u003e \u003cp\u003e5.4 Hepatic Elimination and Clearance 119\u003c\/p\u003e \u003cp\u003e5.4.1 Phase I and Phase II Metabolism 120\u003c\/p\u003e \u003cp\u003e5.4.2 The Cytochrome P450 Enzyme System 121\u003c\/p\u003e \u003cp\u003e5.4.3 Glucuronidation 122\u003c\/p\u003e \u003cp\u003e5.4.4 Metabolism-Based Drug–Drug Interactions 122\u003c\/p\u003e \u003cp\u003e5.4.5 Hepatic Drug Transporters and Drug–Drug Interactions 125\u003c\/p\u003e \u003cp\u003e5.4.6 Kinetics of Drug Metabolism 127\u003c\/p\u003e \u003cp\u003e5.4.7 Hepatic Clearance and Related Parameters 128\u003c\/p\u003e \u003cp\u003eProblems 139\u003c\/p\u003e \u003cp\u003eReferences 142\u003c\/p\u003e \u003cp\u003e\u003cb\u003e6 Compartmental Models in Pharmacokinetics 145\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eSara E. Rosenbaum\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e6.1 Introduction 146\u003c\/p\u003e \u003cp\u003e6.2 Expressions for Component Parts of the Dose–Plasma Concentration Relationship 146\u003c\/p\u003e \u003cp\u003e6.2.1 Effective Dose 146\u003c\/p\u003e \u003cp\u003e6.2.2 Rate of Drug Absorption 147\u003c\/p\u003e \u003cp\u003e6.2.3 Rate of Drug Elimination 148\u003c\/p\u003e \u003cp\u003e6.2.4 Rate of Drug Distribution 148\u003c\/p\u003e \u003cp\u003e6.3 Putting Everything Together: Compartments and Models 149\u003c\/p\u003e \u003cp\u003e6.3.1 One-Compartment Model 149\u003c\/p\u003e \u003cp\u003e6.3.2 Two-Compartment Model 150\u003c\/p\u003e \u003cp\u003e6.3.3 Three-Compartment Model 150\u003c\/p\u003e \u003cp\u003e6.4 Examples of Complete Compartment Models 152\u003c\/p\u003e \u003cp\u003e6.4.1 Intravenous Bolus Injection in a One-Compartment Model with First-Order Elimination 152\u003c\/p\u003e \u003cp\u003e6.4.2 Intravenous Bolus Injection in a Two-Compartment Model with First-Order Elimination 153\u003c\/p\u003e \u003cp\u003e6.4.3 First-Order Absorption in a Two-Compartment Model with First-Order Elimination 154\u003c\/p\u003e \u003cp\u003e6.5 Use of Compartmental Models to Study Metabolite Pharmacokinetics 155\u003c\/p\u003e \u003cp\u003e6.6 Selecting and Applying Models 156\u003c\/p\u003e \u003cp\u003eProblems 157\u003c\/p\u003e \u003cp\u003eSuggested Readings 157\u003c\/p\u003e \u003cp\u003e\u003cb\u003e7 Pharmacokinetics of an Intravenous Bolus Injection in a One-Compartment Model 159\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eSara E. Rosenbaum\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e7.1 Introduction 160\u003c\/p\u003e \u003cp\u003e7.2 One-Compartment Model 160\u003c\/p\u003e \u003cp\u003e7.3 Pharmacokinetic Equations 162\u003c\/p\u003e \u003cp\u003e7.3.1 Basic Equation 162\u003c\/p\u003e \u003cp\u003e7.3.2 Half-Life 163\u003c\/p\u003e \u003cp\u003e7.3.3 Time to Eliminate a Dose 163\u003c\/p\u003e \u003cp\u003e7.4 Simulation Exercise 163\u003c\/p\u003e \u003cp\u003e7.5 Application of the Model 165\u003c\/p\u003e \u003cp\u003e7.5.1 Predicting Plasma Concentrations 165\u003c\/p\u003e \u003cp\u003e7.5.2 Duration of Action 166\u003c\/p\u003e \u003cp\u003e7.5.3 Value of a Dose to Give a Desired Initial Plasma Concentration 167\u003c\/p\u003e \u003cp\u003e7.5.4 Intravenous Loading Dose 167\u003c\/p\u003e \u003cp\u003e7.6 Determination of Pharmacokinetic Parameters Experimentally 168\u003c\/p\u003e \u003cp\u003e7.6.1 Study Design for the Determination of Parameters 168\u003c\/p\u003e \u003cp\u003e7.6.2 Pharmacokinetic Analysis 169\u003c\/p\u003e \u003cp\u003e7.7 Pharmacokinetic Analysis in Clinical Practice 173\u003c\/p\u003e \u003cp\u003eProblems 174\u003c\/p\u003e \u003cp\u003eSuggested Reading 176\u003c\/p\u003e \u003cp\u003e\u003cb\u003e8 Pharmacokinetics of an Intravenous Bolus Injection in a Two-Compartment Model 177\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eSara E. Rosenbaum\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e8.1 Introduction 178\u003c\/p\u003e \u003cp\u003e8.2 Tissue and Compartmental Distribution of a Drug 179\u003c\/p\u003e \u003cp\u003e8.2.1 Drug Distribution to the Tissues 179\u003c\/p\u003e \u003cp\u003e8.2.2 Compartmental Distribution of a Drug 180\u003c\/p\u003e \u003cp\u003e8.3 Basic Equation 181\u003c\/p\u003e \u003cp\u003e8.3.1 Distribution: \u003ci\u003eA,\u003c\/i\u003e α, and the Distribution \u003ci\u003et\u003c\/i\u003e\u003csub\u003e1\/2\u003c\/sub\u003e 182\u003c\/p\u003e \u003cp\u003e8.3.2 Elimination: \u003ci\u003eB,\u003c\/i\u003e β, and the β \u003ci\u003et\u003c\/i\u003e\u003csub\u003e1\/2\u003c\/sub\u003e 182\u003c\/p\u003e \u003cp\u003e8.4 Relationship Between Macro and Micro Rate Constants 183\u003c\/p\u003e \u003cp\u003e8.5 Primary Pharmacokinetic Parameters 183\u003c\/p\u003e \u003cp\u003e8.5.1 Clearance 184\u003c\/p\u003e \u003cp\u003e8.5.2 Distribution Clearance 184\u003c\/p\u003e \u003cp\u003e8.5.3 Volume of Distribution 186\u003c\/p\u003e \u003cp\u003e8.6 Simulation Exercise 188\u003c\/p\u003e \u003cp\u003e8.7 Determination of the Pharmacokinetic Parameters of the Two-Compartment Model 191\u003c\/p\u003e \u003cp\u003e8.7.1 Determination of Intercepts and Macro Rate Constants 191\u003c\/p\u003e \u003cp\u003e8.7.2 Determination of the Micro Rate Constants: \u003ci\u003ek\u003c\/i\u003e\u003csub\u003e12\u003c\/sub\u003e \u003ci\u003ek\u003c\/i\u003e\u003csub\u003e21\u003c\/sub\u003e and \u003ci\u003ek\u003c\/i\u003e\u003csub\u003e10\u003c\/sub\u003e 193\u003c\/p\u003e \u003cp\u003e8.7.3 Determination of the Primary Pharmacokinetic Parameters 193\u003c\/p\u003e \u003cp\u003e8.8 Clinical Application of the Two-Compartment Model 194\u003c\/p\u003e \u003cp\u003e8.8.1 Measurement of the Elimination Half-Life in the Postdistribution Phase 194\u003c\/p\u003e \u003cp\u003e8.8.2 Determination of the Loading Dose 195\u003c\/p\u003e \u003cp\u003e8.8.3 Evaluation of a Dose: Monitoring Plasma Concentrations and Patient Response 197\u003c\/p\u003e \u003cp\u003eProblems 197\u003c\/p\u003e \u003cp\u003eSuggested Readings 199\u003c\/p\u003e \u003cp\u003e\u003cb\u003e9 Pharmacokinetics of Extravascular Drug Administration 201\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eDr. Steven C. Sutton\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e9.1 Introduction 202\u003c\/p\u003e \u003cp\u003e9.2 First-Order Absorption in a One-Compartment Model 203\u003c\/p\u003e \u003cp\u003e9.2.1 Model and Equations 203\u003c\/p\u003e \u003cp\u003e9.2.2 Parameter Determination 205\u003c\/p\u003e \u003cp\u003e9.2.3 Absorption Lag Time 210\u003c\/p\u003e \u003cp\u003e9.2.4 Flip-Flop Model and Sustained-Release Preparations 212\u003c\/p\u003e \u003cp\u003e9.2.5 Determinants of \u003ci\u003eT\u003c\/i\u003e\u003csub\u003emax\u003c\/sub\u003e and \u003ci\u003eC\u003c\/i\u003e\u003csub\u003emax\u003c\/sub\u003e 212\u003c\/p\u003e \u003cp\u003e9.3 Modified Release and Gastric Retention Formulations 214\u003c\/p\u003e \u003cp\u003e9.3.1 Impact of the Stomach 214\u003c\/p\u003e \u003cp\u003e9.3.2 Moisture in the Gastrointestinal Tract 215\u003c\/p\u003e \u003cp\u003e9.4 Bioavailability 215\u003c\/p\u003e \u003cp\u003e9.4.1 Bioavailability Parameters 215\u003c\/p\u003e \u003cp\u003e9.4.2 Absolute Bioavailability 217\u003c\/p\u003e \u003cp\u003e9.4.3 Relative Bioavailability 217\u003c\/p\u003e \u003cp\u003e9.4.4 Bioequivalence 217\u003c\/p\u003e \u003cp\u003e9.4.5 Single-Dose Crossover Parallel and Steady-State Study Designs 219\u003c\/p\u003e \u003cp\u003e9.4.6 Example Bioavailability Analysis 219\u003c\/p\u003e \u003cp\u003e9.5 \u003ci\u003eIn Vitro-In Vivo \u003c\/i\u003eCorrelation 219\u003c\/p\u003e \u003cp\u003e9.5.1 Definitions 219\u003c\/p\u003e \u003cp\u003e9.5.2 Assumptions 220\u003c\/p\u003e \u003cp\u003e9.5.3 Utility 220\u003c\/p\u003e \u003cp\u003e9.5.4 Immediate Release IVIVC 220\u003c\/p\u003e \u003cp\u003e9.5.5 Modified Release IVIVC 221\u003c\/p\u003e \u003cp\u003e9.6 Simulation Exercise 222\u003c\/p\u003e \u003cp\u003eProblems 223\u003c\/p\u003e \u003cp\u003eReferences 224\u003c\/p\u003e \u003cp\u003e\u003cb\u003e10 Introduction to Noncompartmental Analysis 225\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eSara E. Rosenbaum\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e10.1 Introduction 225\u003c\/p\u003e \u003cp\u003e10.2 Mean Residence Time 226\u003c\/p\u003e \u003cp\u003e10.3 Determination of Other Important Pharmacokinetic Parameters 229\u003c\/p\u003e \u003cp\u003e10.4 Different Routes of Administration 231\u003c\/p\u003e \u003cp\u003e10.5 Application of Noncompartmental Analysis to Clinical Studies 232\u003c\/p\u003e \u003cp\u003eProblems 234\u003c\/p\u003e \u003cp\u003e\u003cb\u003e11 Pharmacokinetics of Intravenous Infusion in a One-Compartment Model 237\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eSara E. Rosenbaum\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e11.1 Introduction 238\u003c\/p\u003e \u003cp\u003e11.2 Model and Equations 239\u003c\/p\u003e \u003cp\u003e11.2.1 Basic Equation 239\u003c\/p\u003e \u003cp\u003e11.2.2 Application of the Basic Equation 241\u003c\/p\u003e \u003cp\u003e11.2.3 Simulation Exercise: Part 1 241\u003c\/p\u003e \u003cp\u003e11.3 Steady-State Plasma Concentration 242\u003c\/p\u003e \u003cp\u003e11.3.1 Equation for Steady-State Plasma Concentrations 242\u003c\/p\u003e \u003cp\u003e11.3.2 Application of the Equation 242\u003c\/p\u003e \u003cp\u003e11.3.3 Basic Formula Revisited 243\u003c\/p\u003e \u003cp\u003e11.3.4 Factors Controlling Steady-State Plasma Concentration 243\u003c\/p\u003e \u003cp\u003e11.3.5 Time to Steady State 244\u003c\/p\u003e \u003cp\u003e11.3.6 Simulation Exercise: Part 2 245\u003c\/p\u003e \u003cp\u003e11.4 Loading Dose 246\u003c\/p\u003e \u003cp\u003e11.4.1 Loading-Dose Equation 246\u003c\/p\u003e \u003cp\u003e11.4.2 Simulation Exercise: Part 3 248\u003c\/p\u003e \u003cp\u003e11.5 Termination of Infusion 248\u003c\/p\u003e \u003cp\u003e11.5.1 Equations for Termination Before and After Steady State 248\u003c\/p\u003e \u003cp\u003e11.5.2 Simulation Exercise: Part 4 249\u003c\/p\u003e \u003cp\u003e11.6 Individualization of Dosing Regimens 249\u003c\/p\u003e \u003cp\u003e11.6.1 Initial Doses 249\u003c\/p\u003e \u003cp\u003e11.6.2 Monitoring and Individualizing Therapy 250\u003c\/p\u003e \u003cp\u003eProblems 252\u003c\/p\u003e \u003cp\u003e\u003cb\u003e12 Multiple Intravenous Bolus Injections in the One-Compartment Model 255\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eSara E. Rosenbaum\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e12.1 Introduction 256\u003c\/p\u003e \u003cp\u003e12.2 Terms and Symbols Used in Multiple-Dosing Equations 257\u003c\/p\u003e \u003cp\u003e12.3 Monoexponential Decay During a Dosing Interval 259\u003c\/p\u003e \u003cp\u003e12.3.1 Calculation of Dosing Interval to Give Specific Steady-State Peaks and Troughs 260\u003c\/p\u003e \u003cp\u003e12.4 Basic Pharmacokinetic Equations for Multiple Doses 260\u003c\/p\u003e \u003cp\u003e12.4.1 Principle of Superposition 260\u003c\/p\u003e \u003cp\u003e12.4.2 Equations that Apply Before Steady State 261\u003c\/p\u003e \u003cp\u003e12.5 Steady State 262\u003c\/p\u003e \u003cp\u003e12.5.1 Steady-State Equations 263\u003c\/p\u003e \u003cp\u003e12.5.2 Average Plasma Concentration at Steady State 264\u003c\/p\u003e \u003cp\u003e12.5.3 Fluctuation 267\u003c\/p\u003e \u003cp\u003e12.5.4 Accumulation 267\u003c\/p\u003e \u003cp\u003e12.5.5 Time to Reach Steady State 269\u003c\/p\u003e \u003cp\u003e12.5.6 Loading Dose 270\u003c\/p\u003e \u003cp\u003e12.6 Basic Formula Revisited 270\u003c\/p\u003e \u003cp\u003e12.7 Pharmacokinetic-Guided Dosing Regimen Design 270\u003c\/p\u003e \u003cp\u003e12.7.1 General Considerations for Selection of the Dosing Interval 270\u003c\/p\u003e \u003cp\u003e12.7.2 Protocols for Pharmacokinetic-Guided Dosing Regimens 272\u003c\/p\u003e \u003cp\u003e12.8 Simulation Exercise 276\u003c\/p\u003e \u003cp\u003eProblems 277\u003c\/p\u003e \u003cp\u003eReference 278\u003c\/p\u003e \u003cp\u003e\u003cb\u003e13 Multiple Intermittent Infusions 279\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eSara E. Rosenbaum\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e13.1 Introduction 279\u003c\/p\u003e \u003cp\u003e13.2 Steady-State Equations for Multiple Intermittent Infusions 281\u003c\/p\u003e \u003cp\u003e13.3 Monoexponential Decay During a Dosing Interval: Determination of Peaks Troughs and Elimination Half-Life 284\u003c\/p\u003e \u003cp\u003e13.3.1 Determination of Half-Life 284\u003c\/p\u003e \u003cp\u003e13.3.2 Determination of Peaks and Troughs 286\u003c\/p\u003e \u003cp\u003e13.4 Determination of the Volume of Distribution 286\u003c\/p\u003e \u003cp\u003e13.5 Individualization of Dosing Regimens 289\u003c\/p\u003e \u003cp\u003e13.6 Simulation 289\u003c\/p\u003e \u003cp\u003eProblems 290\u003c\/p\u003e \u003cp\u003e\u003cb\u003e14 Multiple Oral Doses 293\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eSara E. Rosenbaum\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e14.1 Introduction 293\u003c\/p\u003e \u003cp\u003e14.2 Steady-State Equations 294\u003c\/p\u003e \u003cp\u003e14.2.1 Time to Peak Steady-State Plasma Concentration 295\u003c\/p\u003e \u003cp\u003e14.2.2 Maximum Steady-State Plasma Concentration 296\u003c\/p\u003e \u003cp\u003e14.2.3 Minimum Steady-State Plasma Concentration 296\u003c\/p\u003e \u003cp\u003e14.2.4 Average Steady-State Plasma Concentration 296\u003c\/p\u003e \u003cp\u003e14.2.5 Overall Effect of Absorption Parameters on a Steady-State Dosing Interval 297\u003c\/p\u003e \u003cp\u003e14.3 Equations Used Clinically to Individualize Oral Doses 298\u003c\/p\u003e \u003cp\u003e14.3.1 Protocol to Select an Appropriate Equation 298\u003c\/p\u003e \u003cp\u003e14.4 Simulation Exercise 300\u003c\/p\u003e \u003cp\u003eReferences 301\u003c\/p\u003e \u003cp\u003e\u003cb\u003e15 Nonlinear Pharmacokinetics 303\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eSara E. Rosenbaum\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e15.1 Linear Pharmacokinetics 304\u003c\/p\u003e \u003cp\u003e15.2 Nonlinear Processes in Absorption, Distribution, Metabolism, and Elimination 306\u003c\/p\u003e \u003cp\u003e15.3 Pharmacokinetics of Capacity-Limited Metabolism 307\u003c\/p\u003e \u003cp\u003e15.3.1 Kinetics of Enzymatic Processes 307\u003c\/p\u003e \u003cp\u003e15.3.2 Plasma Concentration–Time Profile 309\u003c\/p\u003e \u003cp\u003e15.4 Phenytoin 310\u003c\/p\u003e \u003cp\u003e15.4.1 Basic Equation for Steady State 311\u003c\/p\u003e \u003cp\u003e15.4.2 Estimation of Doses and Plasma Concentrations 313\u003c\/p\u003e \u003cp\u003e15.4.3 Influence of \u003ci\u003eK\u003csub\u003em\u003c\/sub\u003e \u003c\/i\u003eand \u003ci\u003eV\u003c\/i\u003e\u003csub\u003emax\u003c\/sub\u003e and Factors That Affect These Parameters 314\u003c\/p\u003e \u003cp\u003e15.4.4 Time to Eliminate the Drug 316\u003c\/p\u003e \u003cp\u003e15.4.5 Time to Reach Steady State 317\u003c\/p\u003e \u003cp\u003e15.4.6 Individualization of Doses of Phenytoin 318\u003c\/p\u003e \u003cp\u003eProblems 321\u003c\/p\u003e \u003cp\u003eReferences 322\u003c\/p\u003e \u003cp\u003e\u003cb\u003e16 Introduction to Pharmacogenetics 323\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eDr. Daniel Brazeau\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e16.1 Introduction 324\u003c\/p\u003e \u003cp\u003e16.2 Genetics Primer 324\u003c\/p\u003e \u003cp\u003e16.2.1 Basic Terminology: Genes Alleles Loci and Polymorphism 324\u003c\/p\u003e \u003cp\u003e16.2.2 Population Genetics: Allele and Genotype Frequencies 326\u003c\/p\u003e \u003cp\u003e16.2.3 Quantitative Genetics and Complex Traits 327\u003c\/p\u003e \u003cp\u003e16.3 Pharmacogenetics 328\u003c\/p\u003e \u003cp\u003e16.3.1 Pharmacogenetics of Drug-Metabolizing Enzymes 330\u003c\/p\u003e \u003cp\u003e16.3.2 Pharmacogenetics of Drug Transporters 333\u003c\/p\u003e \u003cp\u003e16.4 Genetics and Pharmacodynamics 334\u003c\/p\u003e \u003cp\u003e16.4.1 Drug Target Pharmacogenetics 334\u003c\/p\u003e \u003cp\u003e16.5 Summary 335\u003c\/p\u003e \u003cp\u003eReference 335\u003c\/p\u003e \u003cp\u003eSuggested Readings 335\u003c\/p\u003e \u003cp\u003e\u003cb\u003e17 Models Used to Predict Drug–Drug Interactions for Orally Administered Drugs 337\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eSara E. Rosenbaum\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e17.1 Introduction 338\u003c\/p\u003e \u003cp\u003e17.2 Mathematical Models for Inhibitors and Inducers of Drug Metabolism Based on \u003ci\u003eIn Vitro \u003c\/i\u003eData 340\u003c\/p\u003e \u003cp\u003e17.2.1 Reversible Inhibition 340\u003c\/p\u003e \u003cp\u003e17.2.2 Time-Dependent Inhibition 341\u003c\/p\u003e \u003cp\u003e17.2.3 Induction 345\u003c\/p\u003e \u003cp\u003e17.3 Surrogate \u003ci\u003eIn Vivo \u003c\/i\u003eValues for the Unbound Concentration of the Perpetrator at the Site of Action 345\u003c\/p\u003e \u003cp\u003e17.3.1 Surrogate Measures of Hepatic Inhibitor and Inducer Concentrations 346\u003c\/p\u003e \u003cp\u003e17.3.2 Surrogate Measures of Intestinal Inhibitor and Inducer Concentrations 346\u003c\/p\u003e \u003cp\u003e17.4 Models Used to Predict DDIs \u003ci\u003eIn Vivo\u003c\/i\u003e 347\u003c\/p\u003e \u003cp\u003e17.4.1 Introduction 347\u003c\/p\u003e \u003cp\u003e17.4.2 Basic Predictive Models: \u003ci\u003eR \u003c\/i\u003eValues 348\u003c\/p\u003e \u003cp\u003e17.4.3 Predictive Models Incorporating Parallel Pathways of Elimination (\u003ci\u003efm\u003c\/i\u003e) 350\u003c\/p\u003e \u003cp\u003e17.4.4 Models Incorporating Intestinal Extraction 354\u003c\/p\u003e \u003cp\u003e17.4.5 Models Combining Multiple Actions of Perpetrators 358\u003c\/p\u003e \u003cp\u003e17.5 Predictive Models for Transporter-Based DDIs 359\u003c\/p\u003e \u003cp\u003e17.5.1 Kinetics of Drug Transporters 359\u003c\/p\u003e \u003cp\u003e17.6 Application of Physiologically Based Pharmacokinetic Models to DDI Prediction: The Dynamic Approach 362\u003c\/p\u003e \u003cp\u003e17.7 Conclusion 362\u003c\/p\u003e \u003cp\u003eProblems 363\u003c\/p\u003e \u003cp\u003eReferences 364\u003c\/p\u003e \u003cp\u003e\u003cb\u003e18 Introduction to Physiologically Based Pharmacokinetic Modeling 367\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eSara E. Rosenbaum\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e18.1 Introduction 368\u003c\/p\u003e \u003cp\u003e18.2 Components of PBPK Models 369\u003c\/p\u003e \u003cp\u003e18.3 Equations for PBPK Models 369\u003c\/p\u003e \u003cp\u003e18.4 Building a PBPK Model 373\u003c\/p\u003e \u003cp\u003e18.5 Simulations 377\u003c\/p\u003e \u003cp\u003e18.6 Estimation of Human Drug-Specific Parameters 378\u003c\/p\u003e \u003cp\u003e18.6.1 Tissue Plasma Partition Coefficient 379\u003c\/p\u003e \u003cp\u003e18.6.2 Volume of Distribution 379\u003c\/p\u003e \u003cp\u003e18.6.3 Clearance 380\u003c\/p\u003e \u003cp\u003e18.7 More Detailed PBPK Models 381\u003c\/p\u003e \u003cp\u003e18.7.1 Permeability-Limited Distribution 381\u003c\/p\u003e \u003cp\u003e18.7.2 Drug Transporters 383\u003c\/p\u003e \u003cp\u003e18.7.3 Models for Oral Absorption 386\u003c\/p\u003e \u003cp\u003e18.7.4 Reduced Models 387\u003c\/p\u003e \u003cp\u003e18.8 Application of PBPK Models 387\u003c\/p\u003e \u003cp\u003eReferences 388\u003c\/p\u003e \u003cp\u003e\u003cb\u003e19 Introduction to Pharmacodynamic Models and Integrated Pharmacokinetic–Pharmacodynamic Models 391\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eDrs. Diane Mould and Paul Hutson\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e19.1 Introduction 392\u003c\/p\u003e \u003cp\u003e19.2 Classic Pharmacodynamic Models Based on Receptor Theory 393\u003c\/p\u003e \u003cp\u003e19.2.1 Receptor Binding 394\u003c\/p\u003e \u003cp\u003e19.2.2 Concentration-Response Models 395\u003c\/p\u003e \u003cp\u003e19.3 Direct Effect Pharmacodynamic Models 402\u003c\/p\u003e \u003cp\u003e19.3.1 \u003ci\u003eE\u003c\/i\u003e\u003csub\u003emax\u003c\/sub\u003e and Sigmoidal \u003ci\u003eE\u003c\/i\u003e\u003csub\u003emax\u003c\/sub\u003e Models 402\u003c\/p\u003e \u003cp\u003e19.3.2 Inhibitory \u003ci\u003eI\u003c\/i\u003e\u003csub\u003emax\u003c\/sub\u003e and Sigmoidal \u003ci\u003eI\u003c\/i\u003emax Models 404\u003c\/p\u003e \u003cp\u003e19.3.3 Linear Adaptations of the \u003ci\u003eE\u003c\/i\u003emax and \u003ci\u003eI\u003c\/i\u003e\u003csub\u003emax\u003c\/sub\u003e Model 404\u003c\/p\u003e \u003cp\u003e19.4 Integrated PK–PD Models: Intravenous Bolus Injection in the One-Compartment Model and the Sigmoidal \u003ci\u003eE\u003c\/i\u003e\u003csub\u003emax\u003c\/sub\u003e Model 406\u003c\/p\u003e \u003cp\u003e19.4.1 Simulation Exercise 409\u003c\/p\u003e \u003cp\u003e19.5 Pharmacodynamic Drug–Drug Interactions 410\u003c\/p\u003e \u003cp\u003e19.5.1 Simulation Exercise 410\u003c\/p\u003e \u003cp\u003eProblems 411\u003c\/p\u003e \u003cp\u003eReferences 412\u003c\/p\u003e \u003cp\u003e\u003cb\u003e20 Semimechanistic Pharmacokinetic–Pharmacodynamic Models 413\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eDrs. Diane Mould and Paul Hutson\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e20.1 Introduction 414\u003c\/p\u003e \u003cp\u003e20.2 Hysteresis and the Effect Compartment 416\u003c\/p\u003e \u003cp\u003e20.2.1 Simulation Exercise 419\u003c\/p\u003e \u003cp\u003e20.3 Physiological Turnover Models and Their Characteristics 419\u003c\/p\u003e \u003cp\u003e20.3.1 Points of Drug Action 421\u003c\/p\u003e \u003cp\u003e20.3.2 System Recovery After Change in Baseline Value 421\u003c\/p\u003e \u003cp\u003e20.4 Indirect Effect Models 422\u003c\/p\u003e \u003cp\u003e20.4.1 Introduction 422\u003c\/p\u003e \u003cp\u003e20.4.2 Characteristics of Indirect Effect Drug Responses 424\u003c\/p\u003e \u003cp\u003e20.4.3 Characteristics of Indirect Effect Models Illustrated Using Model I 426\u003c\/p\u003e \u003cp\u003e20.5 Other Indirect Effect Models 432\u003c\/p\u003e \u003cp\u003e20.5.1 Transit Compartment Models 435\u003c\/p\u003e \u003cp\u003e20.5.2 Model for Hematological Toxicity of Anticancer Drugs 439\u003c\/p\u003e \u003cp\u003e20.5.3 Alternate Parameterizations of Transit Models 442\u003c\/p\u003e \u003cp\u003e20.6 Models of Tolerance 442\u003c\/p\u003e \u003cp\u003e20.6.1 Introduction to Pharmacologic Tolerance 442\u003c\/p\u003e \u003cp\u003e20.6.2 Counter-Regulatory Force Tolerance Model 444\u003c\/p\u003e \u003cp\u003e20.6.3 Precursor Pool Model of Tolerance 447\u003c\/p\u003e \u003cp\u003e20.7 Irreversible Drug Effects 450\u003c\/p\u003e \u003cp\u003e20.7.1 Application of the Turnover Model to Irreversible Drug Action 450\u003c\/p\u003e \u003cp\u003e20.8 Disease Progression Models 452\u003c\/p\u003e \u003cp\u003e20.8.1 Drug Pharmacokinetics 452\u003c\/p\u003e \u003cp\u003e20.8.2 Pharmacodynamics 452\u003c\/p\u003e \u003cp\u003e20.8.3 Disease Activity Models 453\u003c\/p\u003e \u003cp\u003e20.8.4 Disease Progression Models 453\u003c\/p\u003e \u003cp\u003eProblems 459\u003c\/p\u003e \u003cp\u003eReferences 465\u003c\/p\u003e \u003cp\u003e\u003cb\u003eAppendix A Review of Exponents and Logarithms 469\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eSara E. Rosenbaum\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003eA.1 Exponents 469\u003c\/p\u003e \u003cp\u003eA.2 Logarithms: Log and Ln 470\u003c\/p\u003e \u003cp\u003eA.3 Performing Calculations in the Logarithmic Domain 471\u003c\/p\u003e \u003cp\u003eA.3.1 Multiplication 471\u003c\/p\u003e \u003cp\u003eA.3.2 Division 472\u003c\/p\u003e \u003cp\u003eA.3.3 Reciprocals 472\u003c\/p\u003e \u003cp\u003eA.3.4 Exponents 472\u003c\/p\u003e \u003cp\u003eA.4 Calculations Using Exponential Expressions and Logarithms 472\u003c\/p\u003e \u003cp\u003eA.5 Decay Function: \u003ci\u003ee\u003c\/i\u003e\u003csup\u003e−\u003ci\u003ekt\u003c\/i\u003e\u003c\/sup\u003e 474\u003c\/p\u003e \u003cp\u003eA.6 Growth Function: 1 − \u003ci\u003ee\u003c\/i\u003e\u003csup\u003e−\u003ci\u003ekt\u003c\/i\u003e\u003c\/sup\u003e 475\u003c\/p\u003e \u003cp\u003eA.7 Decay Function in Pharmacokinetics 475\u003c\/p\u003e \u003cp\u003eProblems 476\u003c\/p\u003e \u003cp\u003e\u003cb\u003eAppendix B Rates of Processes 479\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eSara E. Rosenbaum\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003eB.1 Introduction 479\u003c\/p\u003e \u003cp\u003eB.2 Order of a Rate Process 480\u003c\/p\u003e \u003cp\u003eB.3 Zero-Order Processes 480\u003c\/p\u003e \u003cp\u003eB.3.1 Equation for Zero-Order Filling 480\u003c\/p\u003e \u003cp\u003eB.3.2 Equation for Zero-Order Emptying 481\u003c\/p\u003e \u003cp\u003eB.3.3 Time for Zero-Order Emptying to Go to 50% Completion 481\u003c\/p\u003e \u003cp\u003eB.4 First-Order Processes 482\u003c\/p\u003e \u003cp\u003eB.4.1 Equation for a First-Order Process 482\u003c\/p\u003e \u003cp\u003eB.4.2 Time for 50% Completion: the Half-Life 483\u003c\/p\u003e \u003cp\u003eB.5 Comparison of Zero- and First-Order Processes 484\u003c\/p\u003e \u003cp\u003eB.6 Detailed Example of First-Order Decay in Pharmacokinetics 484\u003c\/p\u003e \u003cp\u003eB.6.1 Equations and Semilogarithmic Plots 484\u003c\/p\u003e \u003cp\u003eB.6.2 Half-Life 485\u003c\/p\u003e \u003cp\u003eB.6.3 Fraction or Percent Completion of a First-Order Process Using First-Order Elimination as an Example 485\u003c\/p\u003e \u003cp\u003eB.7 Examples of the Application of First-Order Kinetics to Pharmacokinetics 487\u003c\/p\u003e \u003cp\u003e\u003cb\u003eAppendix C Creation of Excel Worksheets for Pharmacokinetic Analysis 489\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eSara E. Rosenbaum\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003eC.1 Measurement of AUC and Clearance 489\u003c\/p\u003e \u003cp\u003eC.1.1 Trapezoidal Rule 490\u003c\/p\u003e \u003cp\u003eC.1.2 Excel Spreadsheet to Determine AUC\u003csub\u003e0→∞\u003c\/sub\u003e and Clearance 491\u003c\/p\u003e \u003cp\u003eC.2 Analysis of Data from an Intravenous Bolus Injection in a One-Compartment Model 494\u003c\/p\u003e \u003cp\u003eC.3 Analysis of Data from an Intravenous Bolus Injection in a Two-Compartment Model 496\u003c\/p\u003e \u003cp\u003eC.4 Analysis of Oral Data in a One-Compartment Model 498\u003c\/p\u003e \u003cp\u003eC.5 Noncompartmental Analysis of Oral Data 501\u003c\/p\u003e \u003cp\u003e\u003cb\u003eAppendix D Derivation of Equations for Multiple Intravenous Bolus Injections 505\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eSara E. Rosenbaum\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003eD.1 Assumptions 505\u003c\/p\u003e \u003cp\u003eD.2 Basic Equation for Plasma Concentration After Multiple Intravenous Bolus Injections 505\u003c\/p\u003e \u003cp\u003eD.3 Steady-State Equations 508\u003c\/p\u003e \u003cp\u003e\u003cb\u003eAppendix E Enzyme Kinetics: Michaelis–Menten Equation and Models for Inhibitors and Inducers of Drug Metabolism 509\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eSara E. Rosenbaum and Roberta S. King\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003eE.1 Kinetics of Drug Metabolism: The Michaelis–Menten Model 510\u003c\/p\u003e \u003cp\u003eE.1.1 Overview 510\u003c\/p\u003e \u003cp\u003eE.1.2 Assumptions for Validity of Michaelis–Menten Model 510\u003c\/p\u003e \u003cp\u003eE.1.3 \u003ci\u003eKm \u003c\/i\u003eand \u003ci\u003eV\u003c\/i\u003emax 511\u003c\/p\u003e \u003cp\u003eE.1.4 Derivation of the Michaelis–Menten Equation 511\u003c\/p\u003e \u003cp\u003eE.1.5 Summary, Practical Considerations, and Interpretations 513\u003c\/p\u003e \u003cp\u003eE.1.6 Relationship Between Intrinsic Clearance and the Michaelis–Menten Parameters 514\u003c\/p\u003e \u003cp\u003eE.2 Effect of Perpetrators of DDI on Enzyme Kinetics and Intrinsic Clearance 515\u003c\/p\u003e \u003cp\u003eE.2.1 Reversible Inhibition 515\u003c\/p\u003e \u003cp\u003eE.2.2 Time-Dependent Inhibition 518\u003c\/p\u003e \u003cp\u003eE.2.3 Enzyme Induction 524\u003c\/p\u003e \u003cp\u003eReferences 526\u003c\/p\u003e \u003cp\u003e\u003cb\u003eAppendix F Summary of the Properties of the Fictitious Drugs Used in the Text 527\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eSara E. Rosenbaum\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003eAppendix G Computer Simulation Models 529\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eSara E. Rosenbaum\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003eGlossary of Terms 531\u003c\/p\u003e \u003cp\u003eIndex 537\u003c\/p\u003e\u003c\/font\u003e\u003c\/p\u003e\r\n\r\n\u003cp\u003e\u003cfont size=\"3\"\u003eSubject Areas: Chemistry [\u003ca title=\"See our other books on Chemistry\" href=\"https:\/\/freshlyprintedbooks.co.uk\/search?q=%22Chemistry%20%5BPN%5D%22\"\u003ePN\u003c\/a\u003e]\u003c\/font\u003e\u003c\/p\u003e\r\n\r\n\r\n\u003c\/font\u003e","brand":"Wiley","offers":[{"title":"Brand New","offer_id":52453549310232,"sku":"9781119143154","price":59.29,"currency_code":"GBP","in_stock":true}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/0730\/2037\/5320\/files\/9781119143154.jpg?v=1785286277","url":"https:\/\/freshlyprintedbooks.co.uk\/products\/basic-pharmacokinetics-and-pharmacodynamics-an-integrated-textbook-and-computer-simulations-paperback-softback-9781119143154","provider":"Freshly Printed Books","version":"1.0","type":"link"}