عنوان

Pharmacokinetics of Drugs

شابک

3642786820

شابک

9783642786822

شماره

b556671

عنوان اصلي

Pharmacokinetics of Drugs

نام عام مواد

[Book]

نام نخستين پديدآور

Peter G Welling

نام ناشر، پخش کننده و غيره

Berlin Springer Berlin

تاریخ نشرو بخش و غیره

2013

نام خاص و کميت اثر

XXVI, 537 Seiten in 1 Teil XXVI, 537 Seiten 69 Figuren, 51 tables, 51 schw.-w. Tabellen 235 x 155 mm

عنوان فروست

Handbook of Experimental Pharmacology, 110

متن يادداشت

A. Introduction.- 1 Role of Pharmacokinetics in Drug Discovery and Development.- A. Historical Background.- B. Regulatory Submissions.- C. The Process.- D. Discovery.- E. Preclinical Development.- I. Toxicology and Toxicokinetics.- II. Pharmacokinetic - Pharmacodynamic Relationships.- III. Interactions.- F. Clinical Development.- I. Phase 1.- II. Phase 2.- III. Phase 3.- IV. Interactions.- V. Regulatory Submissions.- G. Postsubmission and Postmarketing Studies.- H. Summary.- References.- B. Analytical Methods.- 2 Contemporary Aspects of Radioimmunoassay Development for Drug Analysis.- A. Introduction.- B. Synthesis of Drug Derivatives for Immunogen Preparation.- I. Coupling of Hapten Carboxyl Group to Carrier Protein.- II. Addition of Carboxyl to Existing Functional Group.- III. Addition of a Functional Group for Bridge to Carboxylic Acid.- IV. Altering the Basic Structure of the Hapten.- C. Immunogen Preparation.- I. Hapten-Carrier Protein Ratios.- II. Carrier Protein Characteristics.- D. Immunization Considerations.- I. Species Effects.- II. Use of Adjuvants.- III. Immunization Sites and Schedules.- E. Matrix Effects of Biological Fluids.- I. Methods for Sample Matrix Effect Elimination.- 1. Filtration/Precipitation of Protein.- 2. Solvent Extraction.- 3. Solid Phase Chromatographic Extraction.- 4. High-Performance Liquid Chromatographic Sample Preparation.- II. Elimination of Sample Matrix Effect by Sample Size.- F. The Suitability of Radioimmunoassay for Drug Analysis.- References.- 3 Mass Spectrometry in Drug Disposition and Pharmacokinetics.- A. Introduction.- B. Ionization Techniques.- I. Electron Ionization.- II. Positive Chemical Ionization.- III. Electron Capture Negative Chemical Ionization.- IV. Liquid Secondary Ion/Fast Atom Bombardment.- V. Thermospray.- VI. Atmospheric Pressure Ionization.- VII. Collision-Induced Dissociation.- C. Chromatographic Techniques.- I. Gas Chromatography/Mass Spectrometry.- II. Liquid Chromatography /Mass Spectrometry.- D. Metabolism Studies.- I. In Vitro Studies.- II. In Vivo Studies in Animal Models.- III. In Vivo Studies in Humans.- E. Pharmacokinetic Studies.- I. Introduction.- II. Animal Models.- III. Humans.- F. Summary.- References.- 4 Analytical Methods for Biotechnology Products.- A. Introduction.- B. Methods.- I. Radiolabels.- 1. Selection of Radiolabel.- 2. Whole-Body Autoradiography.- 3. Radiolabel Realities.- II. Immunoassays.- 1. Enzyme Immunoassays.- 2. Radiolabel-Based Immunoassays.- 3. Immunoassay Limitations.- 4. Immunoassay Interferences.- III. Bioassays.- IV. Other Immunological Techniques.- V. Chromatography.- VI. Electrophoretic Techniques.- VII. Mass Spectrometry.- C. Conclusions.- References.- C. In Vitro Methods-Protein and Tissue Binding.- 5 Metabolism: Scaling-up from In Vitro to Organ and Whole Body.- A. Introduction.- B. Correlation of In Vitro and In Vivo Data.- I. Concept of Organ Clearance.- 1. Hepatic Clearance Models.- 2. In Vitro-Organ Correlations.- II. Concept of Total Body Clearance.- 1. From In Vitro to In Vivo: Compartmental Modeling.- 2. From In Vitro to In Vivo: Physiological Modeling.- 3. From Perfused Organs to In Vivo.- C. Poor Correlations Between In Vitro and Perfused Organs.- I. Inadequacy of In Vitro Estimates.- 1. Estimation of Enzymatic Parameters.- 2. Multiplicity of Enzymes.- 3. Membrane-Bound Enzymes.- 4. Time-Dependent Kinetics.- II. Structural Considerations and Physiological Variables.- 1. Flow.- 2. Protein Binding.- 3. Transmembrane Limitation.- 4. Cosubstrate.- 5. Acinar Heterogeneity.- D. Reasons for Poor Correlations Between In Vitro, Perfused Organs, and In Vivo.- E. Conclusions.- References.- 6 Gastrointestinal Transport of Peptide and Protein Drugs and Prodrugs.- A. Introduction.- B. Mucosal Cell Absorption.- I. Paracellular Absorption.- II. Transcellular Absorption.- 1. Simple Diffusion.- 2. Carrier-Mediated Process.- 3. Endocytosis.- C. Mucosal Cell Transport of Peptide Drugs.- I. Characteristics of Small Peptide Transport.- 1. Substrate Structural Requirements.- II. Carrier-Mediated Transport of Peptide Drugs.- 1. ?-Lactam Antibiotics.- 2. ACE Inhibitors.- D. Estimating Extent of Drug Absorption.- I. Fraction of Dose Absorbed - Permeability Correlation.- II. Comparison of Passive and Carrier-Mediated Transport.- E. Peptide Prodrug Approaches to Improving Intestinal Absorption.- I. Peptide Prodrugs of ?-Methyldopa.- II. Peptide Prodrug Approaches for Acidic Drugs.- III. Other Peptide Prodrugs.- F. Summary.- References.- D. Classical Problems.- 7 Stereoselectivity in Metabolic Reactions of Toxication and Detoxication.- A. Introduction.- B. Principles of Stereoselective Xenobiotic Metabolism.- I. Chiral Recognition and Stereoselective Processes in Xenobiotic Metabolism and Disposition.- II. Substrate Stereoselectivity and Product Stereoselectivity.- III. Substrate-Product Stereoselectivity.- IV. Relevance to Molecular Toxicology.- C. Toxicologically Relevant Examples of Stereoselective Metabolism.- I. Introduction.- II. Substrate Stereoselectivity in Drug Oxidation: Disopyramide and Mianserin.- III. Product Stereoselectivity in Drug Oxidation and Reduction: Phenytoin and Nabilone.- IV. Substrate Stereoselectivity in Xenobiotic Conjugation: Fenvalerate.- D. The Case of Profens.- I. Metabolic Chiral Inversion: In Vivo and In Vitro Studies.- II. Mechanism of Inversion.- III. Toxicological Consequences of Chiral Inversion.- E. Conclusion.- References.- 8 Interethnic Differences in Drug Disposition and Response: Relevance for Drug Development, Licensing, and Registration.- A. Introduction.- B. Case Reports.- I. Unexpected Behavior.- II. A Biopharmaceutical Dilemma.- III. The Drug Which Did Not Become a Case.- IV. The Drug Which Is Not a Case.- C. Basic Concepts and Definitions.- D. Integration of Pharmacokinetic, Pharmacodynamic, and Toxicokinetic Principles in Drug Development.- I. The Conceptual Framework.- II. Preclinical Studies.- III. Phase 1 Studies.- IV. Phase 2 Studies.- V. Phase 3 Clinical Studies.- VI. Regulatory Considerations.- VII. Interethnic Differences in Drug Behavior and Action and PK/PD Integration.- E. Preclinical Studies.- F. Phase 1 Studies and Interethnic Differences.- I. Investigational Pharmacokinetics.- II. Investigational Pharmacodynamics.- III. Bioavailability Investigations.- IV. Bioequivalence Studies.- G. Phase 2 Studies.- H. Phase 3 Studies.- I. Phase 4 Studies in the Context of Drug Product Licensing.- I. Pharmacoanthropological Considerations.- II. Studies in Healthy Volunteers.- III. Studies in Patients.- J. Conclusions.- References.- Appendix. Selected References on Interethnic Differences in Drug Kinetics.- 9 Clinical Relevance of Pharmacogenetics.- A. Introduction.- B. The Genetic Polymorphism of the Sparteine/Debrisoquine Oxidation.- I. Molecular Mechanisms of the Sparteine/Debrisoquine Polymorphism.- II. Clinical Consequences of the Sparteine/Debrisoquine Polymorphism and Assignment of Genotype or Phenotype.- C. The Genetic Polymorphism of Mephenytoin Oxidation.- I. Molecular Mechanisms of the Mephenytoin Polymorphism.- II. Clinical Consequences of Polymorphic Mephenytoin Oxidation and Assignment of Genotype or Phenotype.- D. The Genetic Polymorphism of N-Acetylation.- I. Molecular Mechanisms of Polymorphic N-Acetylation.- II. Clinical Consequences of Polymorphic Acetylation and Assignment of Genotype or Phenotype.- E. Genetic Polymorphisms and Drug Development.- F. Genetic Polymorphisms and Drug Interactions.- G. Conclusions.- References.- 10 Role of Environmental Factors in the Pharmacokinetics of Drugs: Considerations with Respect to Animal Models, P-450 Enzymes, and Probe Drugs.- A. Introduction.- B. Relevant Environmental Factors.- I. What Are "Relevant" Environmental Factors?.- II. Examples.- 1. Cigarette Smoking.- 2. Alcohol Drinking.- 3. Drugs.- 4. Occupational Chemicals.- 5. Other Factors.- C. Animal Models.- I. Environmental Regulation of P-450 Isoforms in the Rat.- II.

متن يادداشت

Hardware and Software Requirements.- C. Directory of Surveyed Software.- D. Conclusion.- References.

متن يادداشت

Similarities and Differences Between Species.- III. Reasons for Interspecies Differences.- IV. Model Experiments in Animals.- D. Important (Iso)enzymes in Man.- I. P-450 Enzymes.- 1. P-450 1A1.- 2. P-450 1A2.- 3. P-450 2A6.- 4. P-450 2B6.- 5. P-450 2C.- 6. P-450 2D6.- 7. P-450 2E1.- 8. P-450 3A.- II. Conjugative Enzymes.- III. Heterologous Expression Systems.- E. Probe Drugs.- I. The Probe Drug Concept.- 1. The "Ideal" Probe Drug.- 2. "General" vs "Specific" Probe Drugs.- II. Importance of Enzyme Specificity.- III. Selected Probe Drugs.- 1. Antipyrine.- 2. Aminopyrine.- 3. Caffeine.- 4. Theophylline.- 5. Nifedipine.- 6. Barbiturates.- 7. Tolbutamide.- 8. Warfarin.- 9. Other Potential Probes.- 10. Endogenous Probes.- IV. Cocktail Approach.- F. Practical Considerations for Human Studies.- G. Final Considerations.- References.- 11 Time Course of Drug Effect.- A. Introduction.- I. Why Prediction of Effect Over Time Is Important.- 1. Drug Development.- 2. Dosage Individualization.- B. Methodological Considerations Relevant to Measuring Effects.- I. Standardization.- II. Continuous Scale Versus Discrete Response.- III. Baseline and Placebo Effect.- C. Pharmacokinetic-Pharmacodynamic Models.- I. Pharmacokinetics.- II. Kietics of Receptor Binding.- III. Steady-State Pharmacodynamic Models.- IV. Non-Steady-State Pharmacodynamic Models.- 1. Effect Compartment.- 2. Physiological Mediator.- V. Placebo Effect.- 1. Pharmacokinetics.- 2. Placebo Effect Model.- 3. Placebo Efficacy.- VI. Disease Time Course and Drug Effects.- 1. Disease Time Course.- 2. Models of Drug Effect on Disease Progression.- VII. Tolerance.- 1. Pharmacokinetics.- 2. Pharmacodynamics.- D. Conclusion.- References.- E. Future Trends in Pharmacokinetics.- 12 Biotechnology Products.- A. Introduction.- B. Pharmacokinetic/Pharmacodynamic Studies.- I. Oligonucleotides.- II. Proteins.- 1. Insulin.- 2. Relaxin.- 3. Interferon-?-2A.- C. Regimen-Dependent Effects.- I. Growth Hormone.- II. Parathyroid Hormone.- III. Tissue Plasminogen Activator.- D. Binding Proteins/Inhibitors.- I. Growth Hormone.- II. Tissue Plasminogen Activator.- III. Insulin-like Growth Factor-I.- IV. Deoxyribonuclease.- E. Catabolism of Biotechnology Products.- I. Catabolism at Extravascular Sites of Administration.- F. Drug Interactions.- References.- 13 Peptide and Protein Drugs.- A. Introduction.- I. Differences Between the Pharmacokinetics of Peptides/Proteins and Other Drugs.- II. Scope of This Review.- B. Pharmacokinetic Mechanisms.- I. Distribution in the Body.- II. Inactivation and Elimination.- 1. Glomerular Filtration.- 2. Peptidolysis.- 3. Receptor-Mediated Clearance.- III. Uptake from Site of Administration.- 1. Subcutaneous or Intramuscular Injection.- 2. Intranasal Administration.- 3. Oral or Rectal Administration.- IV. Pharmacokinetic Behavior Resulting from the Distribution and Elimination Processes.- C. Experimental Approaches.- I. Analytical Methods.- 1. Ex Vivo Bioassay.- 2. Radioimmunoassay.- 3. Radiolabeling.- 4. High-Performance Liquid Chromatography.- 5. Radiosequencing.- II. Plasma Pharmacokinetics.- 1. Intravenous Bolus and Infusion Studies.- 2. Methods of Assaying Samples.- 3. Information That can Be Derived from Plasma Pharmacokinetic Studies.- 4. Use of Organ Ablation to Locate Clearance Sites.- III. Distribution, Metabolism, and Elimination.- 1. Typical Experiments and Results.- 2. Difficulties in Interpreting Results.- 3. Problems in Carrying Out Drug Elimination Studies.- IV. Organ Clearance.- V. Receptor-Mediated Clearance Kinetics.- VI. Absorption (Bioavailability) Measurement.- 1. Oral Route.- 2. Nasal Route.- D. Conclusions.- References.- 14 Toxicokinetics.- A. Introduction.- B. Principles of Toxicokinetics.- C. Bioanalytical Procedures to Support Toxicokinetic Studies.- D. Dose-Plasma Concentration Relationship (Linear-Nonlinear Kinetics).- E. Changes in Concentrations upon Multiple Dosing.- F. Designing Troubleshooting Studies to Explain Aberrant Data.- I. Absorption Issues.- 1. Dose Proportionality.- 2. Effect of Diet.- 3. Effect of Vehicles.- II. Metabolism Issues.- 1. Enzyme Induction.- 2. Effect of Age.- 3. Sex Dependency.- G. Species Comparisons and Interspecies (Allometric) Scaling.- H. Utilization of Pharmacokinetic/Toxicokinetic Data in the Design of Early Clinical Trials.- References.- 15 The Population Approach: Rationale, Methods, and Applications in Clinical Pharmacology and Drug Development.- A. Introduction.- B. Rationale.- I. "Population Studies" in Large Samples of Subjects.- II. Controlled Experimental Studies in Small Groups.- III. The Population Approach.- C. An Overview of Statistical Methodology for Model-Based Population Analysis.- I. Population Model.- II. Population Methods for Data Analysis.- III. Synthesis.- D. Current Experience with the Population Approach and Its Applications to Drug Therapy.- I. Introduction.- II. Detection of Patient Groups with Altered Kinetics.- III. Design of Optimum A Priori Dosage Regimen..- IV. Bayesian Estimation of Individual Pharmacokinetic Parameters.- V. Recent Novel Applications of Nonlinear Mixed Effects Models to Other Drug-Related Areas.- E. Problems and Issues?.- I. Misconceptions.- II. Some Practical Problems.- 1. Reliability of Data and Analysis.- 2. Methodological Issues.- III. Validation of the Results.- F. Integration of the Population Approach into Clinical Drug Development.- I. Introduction.- II. Early Human Studies (Phase I).- III. Early Clinical Studies (Phase II).- IV. Clinical Trials (Late Phase II, Phase III).- V. Late Clinical Trials (Late Phase III, Phase IV).- G. Concluding Remarks.- References.- F. Impact of New Methods on Pharmacokinetics.- 16 Contribution of Positron Emission Tomography to Pharmacokinetic Studies.- A. Introduction.- B. Positron Emitters.- C. Drug Labeling - Radiochemistry.- D. Positron Emission Tomography.- E. Direct Radiolabeled Drug Studies.- I. Drug Distribution.- II. Drug-Drug and Drug-Nutrient Interactions.- III. Drug-Receptor Interactions.- 1. Tranquilizers.- 2. Neuroleptics.- F. Indirect Radioactive Pharmacokinetic Studies.- G. Kinetic Modeling with PET.- I. A Two-Compartment Model: the [15O] Water Model.- II. A Three-Compartment Linear Model: the [18F] Fluorodeoxyglucose Model.- III. A Multicompartment Nonlinear Model: the Ligand- Receptor Model.- IV. Modeling Using Simplified Models.- V. Modeling Using the Multi-injection Approach.- H. Conclusion.- References.- 17 In Vivo Imaging in Drug Discovery and Design.- A. Introduction.- B. Pharmacokinetics.- I. Antimicrobial Agents.- 1. Erythromycin.- 2. Fluconazole.- II. Antineoplastic Agents.- 1. Platinum Compounds.- 2. 5-Fluorouracil.- III. Neuroleptics.- IV. Angiotensin-Converting Enzyme Inhibitors.- V. Nuclear Magnetic Resonance.- C. Pharmacodynamics.- I. Cardiovascular.- 1. Ventricular Function.- 2. Blood Volume.- 3. Cardiac Output.- II. Renal Perfusion and Function.- III. Antineoplastic Agents.- IV. Liver Function.- V. Intestinal Function.- VI. Antimicrobial Agents.- VII. Nuclear Magnetic Resonance.- D. Summary.- References.- G. Appendix.- 18 Considerations on Data Analysis Using Computer Methods and Currently Available Software for Personal Computers.- A. Introduction.- B. Program Features and Requirements.- I. Data Entry.- II. Pharmacokinetic Model Specification.- 1. Compartmental Models.- 2. Noncompartmental Approach.- 3. Pharmacodynamic Models.- 4. Absorption Kinetics and Bioavailability Studies.- 5. Urinary Data Analysis.- 6. Population Pharmacokinetics.- 7. Calculation of Individual Dosage Regimen.- III. Error Model specification.- IV. Parameter Estimation.- 1. Least-Squares and Maximum Likelihood Estimators.- 2. Linear Equations.- 3. Nonlinear Equations.- V. Confidence Limits on Estimated Parameters.- VI. Statistical Measures of Goodness of Fit.- VII. Solving Systems of Differential Equations.- VIII. Graphic Display of Results.- IX. Printing and Plotting Results.- X. User Interface and Documentation.- XI.

شماره رده

نشانه اثر

مستند نام اشخاص تاييد نشده

Peter G Welling

مستند نام اشخاص تاييد نشده

Peter G Welling

نام الکترونيکي

نوع ماده

[Book]

تكميل شده

Y