Principles of Clinical Pharmacology

This revised second edition covers the pharmacologic principles underlying the individualization of patient therapy and contemporary drug development, focusing on the fundamentals that underlie the clinical use and contemporary development of pharmaceuticals. Authors drawn from academia, the pharmaceutical industry and government agencies cover the spectrum of material, including pharmacokinetic practice questions, covered by the basic science section of the certifying examination offered by the American Board of Clinical Pharmacology. This unique reference is recommended by the Board as a study text and includes modules on drug discovery and development to assist students as well as practicing pharmacologists. Unique breadth of coverage ranging from drug discovery and development to individualization and quality assessment of drug therapy Unusual cohesive of presentation that stems from author participation in an ongoing popular NIH course Instructive linkage of pharmacokinetic theory and applications with provision of sample problems for self-study Wide-ranging perspective of authors drawn from the ranks of Federal agencies, academia and the pharmaceutical industry Expanded coverage of pharmacogenetics Expanded coverage of drug transporters and their role in interactions Inclusion of new material on enzyme induction mechanisms in chapters on drug metabolism and drug interactions A new chapter on drug discovery that focuses on oncologic agents Inclusion of therapeutic antibodies in chapter on biotechnology products

This revised second edition covers the pharmacologic principles underlying the individualization of patient therapy and contemporary drug development, focusing on the fundamentals that underlie the clinical use and contemporary development of pharmaceuticals. Authors drawn from academia, the pharmaceutical industry and government agencies cover the spectrum of material, including pharmacokinetic practice questions, covered by the basic science section of the certifying examination offered by the American Board of Clinical Pharmacology. This unique reference is recommended by the Board as a study text and includes modules on drug discovery and development to assist students as well as practicing pharmacologists. Unique breadth of coverage ranging from drug discovery and development to individualization and quality assessment of drug therapy Unusual cohesive of presentation that stems from author participation in an ongoing popular NIH course Instructive linkage of pharmacokinetic theory and applications with provision of sample problems for self-study Wide-ranging perspective of authors drawn from the ranks of Federal agencies, academia and the pharmaceutical industry Expanded coverage of pharmacogenetics Expanded coverage of drug transporters and their role in interactions Inclusion of new material on enzyme induction mechanisms in chapters on drug metabolism and drug interactions A new chapter on drug discovery that focuses on oncologic agents Inclusion of therapeutic antibodies in chapter on biotechnology products

1;Front cover;12;Title page;43;Copyright page;54;Table of contents;65;Preface to the First Edition;166;Preface to the Second Edition;167;Contributors;188;CHAPTER 1. Introduction to Clinical Pharmacology;228.1;BACKGROUND;228.2;PHARMACOKINETICS;259;PART I: PHARMACOKINETICS;309.1;CHAPTER 2. Clinical Pharmacokinetics;329.1.1;THE TARGET CONCENTRATION STRATEGY;329.1.2;CONCEPTS UNDERLYING CLINICAL PHARMACOKINETICS;349.1.3;MATHEMATICAL BASIS OF CLINICAL PHARMACOKINETICS;399.2;CHAPTER 3. Compartmental Analysis of Drug Distribution;469.2.1;PHYSIOLOGICAL SIGNIFICANCE OF DRUG DISTRIBUTION VOLUMES;469.2.2;PHYSIOLOGICAL BASIS OF MULTICOMPARTMENTAL MODELS OF DRUG DISTRIBUTION;489.2.3;CLINICAL CONSEQUENCES OF DIFFERENT DRUG DISTRIBUTION PATTERNS;519.2.4;ANALYSIS OF EXPERIMENTAL DATA;529.3;CHAPTER 4. Drug Absorption and Bioavailability;589.3.1;DRUG ABSORPTION;589.3.2;BIOAVAILABILITY;619.3.3;KINETICS OF DRUG ABSORPTION AFTER ORAL ADMINISTRATION;659.4;CHAPTER 5. Effects of Renal Disease on Pharmacokinetics;729.4.1;EFFECTS OF RENAL DISEASE ON DRUG ELIMINATION;739.4.2;EFFECTS OF RENAL DISEASE ON DRUG DISTRIBUTION;769.4.3;EFFECTS OF RENAL DISEASE ON DRUG ABSORPTION;779.5;CHAPTER 6. Pharmacokinetics in Patients Requiring Renal Replacement Therapy;809.5.1;KINETICS OF INTERMITTENT HEMODIALYSIS;809.5.2;KINETICS OF CONTINUOUS RENAL REPLACEMENT THERAPY;869.5.3;CLINICAL CONSIDERATIONS;889.6;CHAPTER 7. Effect of Liver Disease on Pharmacokinetics;949.6.1;HEPATIC ELIMINATION OF DRUGS;949.6.2;EFFECTS OF LIVER DISEASE ON PHARMACOKINETICS;979.6.3;USE OF THERAPEUTIC DRUGS IN PATIENTS WITH LIVER DISEASE;1019.7;CHAPTER 8. Noncompartmental versus Compartmental Approaches to Pharmacokinetic Analysis;1109.7.1;INTRODUCTION;1109.7.2;KINETICS, PHARMACOKINETICS, AND PHARMACOKINETIC PARAMETERS;1119.7.3;NONCOMPARTMENTAL ANALYSIS;1139.7.4;COMPARTMENTAL ANALYSIS;1189.7.5;NONCOMPARTMENTAL VERSUS COMPARTMENTAL MODELS;1239.7.6;CONCLUSION;1269.8;CHAPTER 9. Distributed Models of Drug Kinetics;1289.8.1;INTRODUCTION;1289.8.2;CENTRAL ISSUES;1289.8.3;DRUG MODALITY I: DELIVERY ACROSS A PLANAR - TISSUE INTERFACE;1299.8.4;DRUG MODALITY II: DELIVERY FROM A POINT SOURCE - DIRECT INTERSTITIAL INFUSION;1389.8.5;SUMMARY;1479.9;CHAPTER 10. Population Pharmacokinetics;1509.9.1;INTRODUCTION;1509.9.2;ANALYSIS OF PHARMACOKINETIC DATA;1509.9.3;POPULATION PHARMACOKINETICS;1519.9.4;MODEL APPLICATIONS;1559.9.5;CONCLUSIONS;15910;PART II: DRUG METABOLISM AND TRANSPORT;16210.1;CHAPTER 11. Pathways of Drug Metabolism;16410.1.1;INTRODUCTION;16410.1.2;PHASE I BIOTRANSFORMATIONS;16710.1.3;PHASE II BIOTRANSFORMATIONS (CONJUGATIONS);17710.1.4;ADDITIONAL EFFECTS ON DRUG METABOLISM;18010.2;CHAPTER 12. Methods of Analysis of Drugs and Drug Metabolites;18410.2.1;INTRODUCTION;18410.2.2;CHOICE OF ANALYTICAL METHODOLOGY;18410.2.3;CHROMATOGRAPHIC SEPARATIONS;18510.2.4;ABSORPTION AND EMISSION SPECTROSCOPY;18610.2.5;IMMUNOAFFINITY ASSAYS;18710.2.6;MASS SPECTROMETRY;18810.2.7;EXAMPLES OF CURRENT ASSAY METHODS;19110.3;CHAPTER 13. Clinical Pharmacogenetics;20010.3.1;INTRODUCTION;20010.3.2;HIERARCHY OF PHARMACOGENETIC INFORMATION;20110.3.3;IDENTIFICATION AND SELECTION OF OUTLIERS IN A POPULATION;20210.3.4;EXAMPLES OF IMPORTANT GENETIC POLYMORPHISMS;20410.3.5;CONCLUSIONS AND FUTURE DIRECTIONS;21210.4;CHAPTER 14. Equilibrative and Concentrative Transport Mechanisms;21810.4.1;INTRODUCTION;21810.4.2;MECHANISMS OF TRANSPORT ACROSS BIOLOGICAL MEMBRANES;21810.4.3;DESCRIPTION OF SELECTED MEMBRANE PROTEIN TRANSPORTERS;22510.4.4;ROLE OF TRANSPORTERS IN PHARMACOKINETICS AND DRUG ACTION;23010.4.5;PHARMACOGENETICS AND PHARMACOGENOMICS OF TRANSPORTERS;23610.4.6;FUTURE DIRECTIONS;24110.5;CHAPTER 15. Drug Interactions;25010.5.1;INTRODUCTION;25010.5.2;MECHANISMS OF DRUG INTERACTIONS;25110.5.3;PREDICTION AND CLINICAL MANAGEMENT OF DRUG INTERACTIONS;26310.6;CHAPTER 16. Biochemical Mechanisms of Drug Toxicity;27010.6.1;INTRODUCTION;27010.6.2;DRUG-INDUCED L