Front cover -- Title page -- Copyright page -- Table of contents -- Preface to the First Edition -- Preface to the Second Edition -- Contributors -- CHAPTER 1. Introduction to Clinical Pharmacology -- BACKGROUND -- PHARMACOKINETICS -- PART I: PHARMACOKINETICS -- CHAPTER 2. Clinical Pharmacokinetics -- THE TARGET CONCENTRATION STRATEGY -- CONCEPTS UNDERLYING CLINICAL PHARMACOKINETICS -- MATHEMATICAL BASIS OF CLINICAL PHARMACOKINETICS -- CHAPTER 3. Compartmental Analysis of Drug Distribution -- PHYSIOLOGICAL SIGNIFICANCE OF DRUG DISTRIBUTION VOLUMES -- PHYSIOLOGICAL BASIS OF MULTICOMPARTMENTAL MODELS OF DRUG DISTRIBUTION -- CLINICAL CONSEQUENCES OF DIFFERENT DRUG DISTRIBUTION PATTERNS -- ANALYSIS OF EXPERIMENTAL DATA -- CHAPTER 4. Drug Absorption and Bioavailability -- DRUG ABSORPTION -- BIOAVAILABILITY -- KINETICS OF DRUG ABSORPTION AFTER ORAL ADMINISTRATION -- CHAPTER 5. Effects of Renal Disease on Pharmacokinetics -- EFFECTS OF RENAL DISEASE ON DRUG ELIMINATION -- EFFECTS OF RENAL DISEASE ON DRUG DISTRIBUTION -- EFFECTS OF RENAL DISEASE ON DRUG ABSORPTION -- CHAPTER 6. Pharmacokinetics in Patients Requiring Renal Replacement Therapy -- KINETICS OF INTERMITTENT HEMODIALYSIS -- KINETICS OF CONTINUOUS RENAL REPLACEMENT THERAPY -- CLINICAL CONSIDERATIONS -- CHAPTER 7. Effect of Liver Disease on Pharmacokinetics -- HEPATIC ELIMINATION OF DRUGS -- EFFECTS OF LIVER DISEASE ON PHARMACOKINETICS -- USE OF THERAPEUTIC DRUGS IN PATIENTS WITH LIVER DISEASE -- CHAPTER 8. Noncompartmental versus Compartmental Approaches to Pharmacokinetic Analysis -- INTRODUCTION -- KINETICS, PHARMACOKINETICS, AND PHARMACOKINETIC PARAMETERS -- NONCOMPARTMENTAL ANALYSIS -- COMPARTMENTAL ANALYSIS -- NONCOMPARTMENTAL VERSUS COMPARTMENTAL MODELS -- CONCLUSION -- CHAPTER 9. Distributed Models of Drug Kinetics -- INTRODUCTION -- CENTRAL ISSUES.

DRUG MODALITY I: DELIVERY ACROSS A PLANAR - TISSUE INTERFACE -- DRUG MODALITY II: DELIVERY FROM A POINT SOURCE - DIRECT INTERSTITIAL INFUSION -- SUMMARY -- CHAPTER 10. Population Pharmacokinetics -- INTRODUCTION -- ANALYSIS OF PHARMACOKINETIC DATA -- POPULATION PHARMACOKINETICS -- MODEL APPLICATIONS -- CONCLUSIONS -- PART II: DRUG METABOLISM AND TRANSPORT -- CHAPTER 11. Pathways of Drug Metabolism -- INTRODUCTION -- PHASE I BIOTRANSFORMATIONS -- PHASE II BIOTRANSFORMATIONS (CONJUGATIONS) -- ADDITIONAL EFFECTS ON DRUG METABOLISM -- CHAPTER 12. Methods of Analysis of Drugs and Drug Metabolites -- INTRODUCTION -- CHOICE OF ANALYTICAL METHODOLOGY -- CHROMATOGRAPHIC SEPARATIONS -- ABSORPTION AND EMISSION SPECTROSCOPY -- IMMUNOAFFINITY ASSAYS -- MASS SPECTROMETRY -- EXAMPLES OF CURRENT ASSAY METHODS -- CHAPTER 13. Clinical Pharmacogenetics -- INTRODUCTION -- HIERARCHY OF PHARMACOGENETIC INFORMATION -- IDENTIFICATION AND SELECTION OF OUTLIERS IN A POPULATION -- EXAMPLES OF IMPORTANT GENETIC POLYMORPHISMS -- CONCLUSIONS AND FUTURE DIRECTIONS -- CHAPTER 14. Equilibrative and Concentrative Transport Mechanisms -- INTRODUCTION -- MECHANISMS OF TRANSPORT ACROSS BIOLOGICAL MEMBRANES -- DESCRIPTION OF SELECTED MEMBRANE PROTEIN TRANSPORTERS -- ROLE OF TRANSPORTERS IN PHARMACOKINETICS AND DRUG ACTION -- PHARMACOGENETICS AND PHARMACOGENOMICS OF TRANSPORTERS -- FUTURE DIRECTIONS -- CHAPTER 15. Drug Interactions -- INTRODUCTION -- MECHANISMS OF DRUG INTERACTIONS -- PREDICTION AND CLINICAL MANAGEMENT OF DRUG INTERACTIONS -- CHAPTER 16. Biochemical Mechanisms of Drug Toxicity -- INTRODUCTION -- DRUG-INDUCED LIVER TOXICITY -- MECHANISMS OF OTHER DRUG TOXICITIES -- PART III: ASSESSMENT OF DRUG EFFECTS -- CHAPTER 17. Physiological and Laboratory Markers of Drug Effect -- BIOLOGICAL MARKERS OF DRUG EFFECT -- IDENTIFICATION AND EVALUATION OF BIOMARKERS.

USES OF BIOMARKERS AND SURROGATE ENDPOINTS -- FUTURE DEVELOPMENT OF BIOMARKERS -- CHAPTER 18. Dose-Effect and Concentration-Effect Analysis -- BACKGROUND -- DRUG-RECEPTOR INTERACTIONS -- GRADED DOSE-EFFECT RELATIONSHIP -- QUANTAL DOSE-EFFECT RELATIONSHIP -- PHARMACODYNAMIC MODELS -- CONCLUSION -- CHAPTER 19. Time Course of Drug Response -- PHARMACOKINETICS AND DELAYED PHARMACOLOGIC EFFECTS -- PHYSIOKINETICS - TIME COURSE OF EFFECTS DUE TO PHYSIOLOGICAL TURNOVER PROCESSES -- THERAPEUTIC RESPONSE, CUMULATIVE DRUG EFFECTS, AND SCHEDULE DEPENDENCE -- CHAPTER 20. Disease Progress Models -- CLINICAL PHARMACOLOGY AND DISEASE PROGRESS -- DISEASE PROGRESS MODELS -- CONCLUSION -- PART IV: OPTIMIZING AND EVALUATING PATIENT THERAPHY -- CHAPTER 21. Pharmacological Differences between Men and Women -- PHARMACOKINETICS -- PHARMACODYNAMICS -- SUMMARY -- CHAPTER 22. Drug Therapy in Pregnant and Nursing Women -- PREGNANCY PHYSIOLOGY AND ITS EFFECTS ON PHARMACOKINETICS -- PHARMACOKINETIC STUDIES DURING PREGNANCY -- PLACENTAL TRANSFER OF DRUGS -- TERATOGENESIS -- DRUG THERAPY IN NURSING MOTHERS -- CHAPTER 23. Drug Therapy in Neonates and Pediatric Patients -- BACKGROUND -- ONTOGENY AND PHARMACOLOGY -- THERAPEUTIC IMPLICATIONS OF GROWTH AND DEVELOPMENT -- CONCLUSIONS -- CHAPTER 24. Drug Therapy in the Elderly -- INTRODUCTION -- PATHOPHYSIOLOGY OF AGING -- AGE-RELATED CHANGES IN PHARMACOKINETICS -- AGE-RELATED CHANGES IN EFFECTOR SYSTEM FUNCTION -- DRUG GROUPS FOR WHICH AGE CONFERS INCREASED RISK FOR TOXICITY -- CONCLUSIONS -- CHAPTER 25. Clinical Analysis of Adverse Drug Reactions -- INTRODUCTION -- CLASSIFICATION -- CLINICAL DETECTION -- ADR DETECTION IN CLINICAL TRIALS -- INFORMATION SOURCES -- CHAPTER 26. Quality Assessment of Drug Therapy -- INTRODUCTION -- ORGANIZATIONAL INFLUENCES ON MEDICATION USE QUALITY -- SUMMARY -- PART V: DRUG DISCOVERY AND DEVELOPMENT.

CHAPTER 27. Portfolio and Project Planning and Management in the Drug Discovery, Development, and Review Process -- INTRODUCTION -- PORTFOLIO DESIGN, PLANNING, AND MANAGEMENT -- PROJECT PLANNING AND MANAGEMENT -- PROJECT PLANNING AND MANAGEMENT TOOLS -- PROJECT TEAM MANAGEMENT AND DECISION-MAKING -- CHAPTER 28. Drug Discovery -- INTRODUCTION -- DEFINITION OF DRUG TARGETS -- GENERATING DIVERSITY -- DEFINITION OF LEAD STRUCTURES -- QUALIFYING LEADS FOR TRANSITION TO EARLY TRIALS -- CHAPTER 29. Preclinical Drug Development -- INTRODUCTION -- COMPONENTS OF PRECLINICAL DRUG DEVELOPMENT -- DRUG DEVELOPMENT PROGRAMS AT THE NCI -- THE CHALLENGE - MOLECULARLY TARGETED THERAPIES AND NEW PARADIGMS FOR CLINICAL TRIALS -- CHAPTER 30. Animal Scale-Up -- INTRODUCTION -- ALLOMETRY -- PHYSIOLOGICAL PHARMACOKINETICS -- IN VITRO-IN VIVO CORRELATION OF HEPATIC METABOLISM -- CHAPTER 31. Phase I Clinical Studies -- INTRODUCTION -- DISEASE-SPECIFIC CONSIDERATIONS -- STARTING DOSE AND DOSE ESCALATION -- BEYOND TOXICITY -- CHAPTER 32. Development of Biotechnology Products and Large Molecules -- INTRODUCTION -- PHARMACOKINETIC CHARACTERISTICS OF MACROMOLECULES -- PHARMACODYNAMICS -- CHAPTER 33. Design of Clinical Development Programs -- INTRODUCTION -- PHASES, SIZE, AND SCOPE OF CLINICAL DEVELOPMENT PROGRAMS -- GOAL AND OBJECTIVES OF CLINICAL DRUG DEVELOPMENT -- CRITICAL DRUG DEVELOPMENT PARADIGMS -- CRITICAL CLINICAL DRUG DEVELOPMENT DECISION POINTS -- LEARNING CONTEMPORARY CLINICAL DRUG DEVELOPMENT -- CHAPTER 34. Role of the FDA in Guiding Drug Development -- WHY DOES THE FDA GET INVOLVED IN DRUG DEVELOPMENT? -- WHEN DOES THE FDA GET INVOLVED IN DRUG DEVELOPMENT? -- HOW DOES THE FDA GUIDE DRUG DEVELOPMENT? -- WHAT ARE FDA GUIDANCES? -- APPENDIX I. Abbreviated Tables of Laplace Transforms -- APPENDIX II. Answers to Study Problems -- Index.