An Integrated Textbook and Computer Simulations
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Köp båda 2 för 1300 krSara 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.
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 1.2.1 Drug Effects at the Site of Action 3 1.2.2 Agonists, Antagonists, and ConcentrationResponse Relationships 6 1.3 Introduction to Pharmacokinetics 9 1.3.1 Plasma Concentration of Drugs 9 1.3.2 Processes in Pharmacokinetics 11 1.4 DoseResponse Relationships 12 1.5 Therapeutic Range 14 1.5.1 Determination of the Therapeutic Range 15 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 2.3.1 Transcellular Passive Diffusion 23 2.3.2 Paracellular Passive Diffusion 25 2.4 Carrier-Mediated Processes: Transport Proteins 26 2.4.1 Uptake Transporters: SLC Superfamily 27 2.4.2 Efflux Transporters: ABC Superfamily 29 2.4.3 Characteristics of Transporter Systems 31 2.4.4 Simulation Exercise 32 2.4.5 Clinical Examples of Transporter Involvement in Drug Response 32 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 3.2.1 Common Routes of Local Drug Administration 37 3.2.2 Common Routes of Systemic Drug Administration 38 3.3 Overview of Oral Absorption 41 3.3.1 Anatomy and Physiology of the Oral-Gastric-Intestinal Tract and Transit Time 41 3.4 Extent of Drug Absorption 44 3.4.1 Bioavailability Factor 44 3.4.2 Individual Bioavailability Factors 45 3.5 Determinants of the Fraction of the Dose Absorbed (F) 46 3.5.1 Disintegration 46 3.5.2 Dissolution 46 3.5.3 Formulation Excipients 50 3.5.4 Adverse Events within the Gastrointestinal Lumen 50 3.5.5 Transcellular Passive Diffusion 53 3.5.6 Particulate Uptake 53 3.5.7 Paracellular Passive Diffusion 53 3.5.8 Uptake and Efflux Transporters 54 3.5.9 Presystemic Intestinal Metabolism or Extraction 58 3.5.10 Presystemic Hepatic Metabolism or Extraction 60 3.6 Factors Controlling the Rate of Drug Absorption 61 3.6.1 Dissolution-Controlled Absorption 63 3.6.2 Membrane Penetration-Controlled Absorption 63 3.6.3 Overall Rate of Drug Absorption 63 3.7 Biopharmaceutics Classification System 64 3.7.1 Intestinal Reserve Length 64 3.7.2 Biopharmaceutics Classification System (BCS) 64 3.7.3 Biopharmaceutics Drug Disposition Classification System (BDDCS) 65 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 4.2.1 Distribution Volumes 74 4.2.2 Tissue Binding Plasma Protein Binding and Partitioning: Concentrating Effects 75 4.2.3 Assessment of the Extent of Drug Distribution: Apparent Volume of Distribution 76 4.2.4 Plasma Protein Binding 82 4.3 Rate of Drug Distribution 89 4.3.1 Perfusion-Controlled Drug Distribution 90 4.3.2 Diffusion or Permeability-Controlled Drug Distribution 93 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 5.1.1 First-Order Elimination 101 5.1.2 Determinants of the Elimination Rate Constant and the Half-Life 102 5.2 Clearance 102 5.2.1 Definition and Determinants of Clearance 102 5.2.2 Total Clearance, Renal Clearance, and Hepatic Clearance 104 5.2.3 Relationships among Clearance, Volume of Distribution, Elimination Rate Constant, and Half-Life 105 5.2.4 Primary and Secondary Parameters 106 5.2.5 Measurement of Total Body Clearance 106 5.3 Renal Clearance 108 5.3.1 Glomerular Filtration 109 5.3.2 Tubular Secretion 110 5.3.3 Tubular Reabsorption 113 5.3.4 Putting Meaning into the Value of Renal Clearance 114 5.3.5 Measurement of Renal Clearance 115 5.3.6 Fraction of the Dose Excreted Unchange