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007			cr mnu
008			050503s2005 flua b 001 0 eng d
010			_a2005048422
020			_a157444882X (alk. paper)
024	3		_a9781574448825
040			_aEG-NcFUE _cEG-NcFUE _dNLM _dBAKER _dC#P _dMUQ _dMXC _erda
042			_apcc
050	0	0	_aRM301.25 _b.P745 2005
060	0	0	_aW1 _bDR893B v.152 2005
060	1	0	_aQV 771 _bP9227 2005
082	0	0	_222 _a615.19 _bP
245	0	0	_aPreclinical drug development / _c[edited by] Mark C. Rogge, David R. Taft
264		1	_aBoca Raton : _bTaylor & Francis, _c2005.
300			_axiv, 575 pages : _billustrations ; _c23 cm
336			_2rdacontent _atext
337			_2rdamedia _aunmediated
338			_2rdacarrier _avolume
440		0	_aDrugs and the pharmaceutical sciences ; _vv. 152
504			_aIncludes bibliographical references and index
505	0		_aFront cover -- Foreword -- Preface -- Contents -- Contributors -- 1 -- The Scope of Preclinical Drug Development: An Introduction and Framework -- REFERENCES -- 2 -- Interspecies Differences in Physiology and Pharmacology: Extrapolating Preclinical Data to Human Populations -- 1. OVERVIEW -- 2. TOXICOLOGY TESTS: POINTS TO CONSIDER -- 3. TOXICOLOGICAL ENDPOINTS -- Table 1 Species-Specific Toxic Effects (4). Reprinted with Permission -- 4. FACTORS THAT CAN INFLUENCE STUDY RESULTS -- Table 2 Correlation of Toxicity to that Observed in Humans (15). Reprinted with -- Table 3 -- 5. INTERSPECIES PHARMACOKINETIC DIFFERENCES 5.1. Drug Absorption -- 5.2. Drug Metabolism -- 5.3. Age-Dependent Changes that can Affect Drug Pharmacokinetics -- Table 4 -- 5.4. Protein Binding Characteristics -- Table 5 Free Fraction of Drugs Across Blood of Various Species -- Table 6 Range of Plasma Protein Values of Eight Mammalian Species -- 5.5. Biliary Excretion -- Table 7 Mean Bile Flow (29). Reprinted with Permission -- 6. ALLOMETRY -- Table 8 Conversion of Body Weight to Surface Area Across Species and Age -- Table 9 Regional Blood Flow Distribution -- 7. CONCLUDING THOUGHTS -- REFERENCES -- 3 -- Transgenic Animals for Preclinical Drug Development -- 1. INTRODUCTION -- 2. PRODUCTION OF TRANSGENIC ANIMALS 2.1. Principles -- 2.2. Experimental Approaches -- 2.3. Gene Targeting -- 2.4. Inducible Gene-Targeting -- 2.5. Addition of Genetic Material into Somatic Cells (Gene Therapy) -- 3. APPLICATIONS IN PRECLINICAL DRUG DEVELOPMENT -- 3.1. Disease Models for Evaluating Biological Activities of New Drugs -- 3.2. Animal Models for Studying Drug Metabolism and Disposition -- 3.3. Animal Models for Evaluating Drug Toxicity/Carcinogenicity -- 4. THE PROSPECTIVE 4.1. Technical Development -- 4.2. Application of Transgenic Technology in Drug Industry -- ACKNOWLEDGMENTS -- REFERENCES. 4 -- Pharmacokinetics/ADME of Small Molecules -- 1. INTRODUCTION -- 2. PHARMACOKINETICS: GENERAL OVERVIEW -- 3. MECHANISMS OF SMALL MOLECULE ABSORPTION -- 3.1. Passive Absorption -- Table 1 Regional Differences in pH and Residence Time Along the Gastrointestinal -- 3.2. Carrier-Mediated Transport -- Table 2 Human Drug Transporters: Standardized Classification According to -- Table 3 Effects of Food and Herbal Products on P-glycoprotein (Pgp) Transport -- 3.3. Bioavailability Determinations -- 4. MECHANISMS OF SMALL MOLECULE DISTRIBUTION -- 5. MECHANISMS OF SMALL MOLECULE METABOLISM -- 5.1. Phase 1 Enzymes -- Table 4 -- Table 5 CYP Phenotyping: Examples of CYP Probe Compounds -- 5.2. Phase 2 Enzymes -- Table 6 Phase 2 Reactions -- Table 7 -- 5.3. Role of Transporters in Drug Metabolism: Synergistic Transport-Metabolism Interactions -- 5.4. Active Metabolites -- 5.5. Physiologic Factors Affecting Drug Metabolism -- 5.6. Metabolic Drug Interactions -- 6. MECHANISMS OF SMALL MOLECULE EXCRETION 6.1. Renal Excretion -- 6.2. Biliary Excretion and Enterohepatic Recycling -- 6.3. Excretion into Breast Milk -- 7. SMALL MOLECULE ADME: ISSUES FOR DRUG DEVELOPMENT 7.1. Pharmacogenetics -- 7.2. Species Differences in Drug Disposition -- Table 8 Species Differences in Hexobarbitone Sleeping Time, Half-Life and -- 7.3. Other Factors Affecting Drug Disposition -- Table 9 -- 8. PHARMACOKINETIC/PHARMACODYNAMIC (PK/PD) MODELING OF PRECLINICAL DATA -- 9. CONCLUSIONS -- REFERENCES -- 5 -- Pharmacokinetics/ADME of Large Molecules -- 1. INTRODUCTION -- 2. CLEARANCE MECHANISMS OF PROTEIN THERAPEUTICS -- 2.1. Proteolysis -- 2.2. Renal Excretion and Metabolism -- Table 1 Clearance Mechanisms for Peptides and Proteins as a Function of Mole-cular -- 2.3. Hepatic Metabolism -- Table 2 -- 2.4. Receptor-Mediated Elimination by Other Cells -- 3. DISTRIBUTION OF PROTEIN THERAPEUTICS. 4. PLASMA PHARMACOKINETICS -- 4.1. Nonlinear Plasma Pharmacokinetics -- 5. PROTEIN BINDING OF PROTEIN THERAPEUTICS -- 6. INTERSPECIES SCALING -- 7. HETEROGENEITY OF PROTEIN THERAPEUTICS -- 8. CHEMICAL MODIFICATIONS OF PROTEIN THERAPEUTICS -- 9. IMMUNOGENICITY -- 10. CONCLUSIONS AND IMPLICATIONS FOR PRECLINICAL DRUG DEVELOPMENT -- REFERENCES -- 6 -- Preclinical Pharmacokinetic- Pharmacodynamic Modeling and Simulation in Drug Development -- 1. INTRODUCTION -- 2. WHAT IS A MODEL AND WHY DO WE DO WE MAKE THEM? -- 3. WHAT CONDITIONS ARE NECESSARY FOR THE PRECLINICAL MODEL TO BE VALID IN HUMANS? -- 4. CASE STUDIES -- 4.1. Case Study 1: Modeling the EEG Effect of Drugs Affecting -- 4.2. Case Study 2: Dose Selection for Phase 1 and 2 Clinical -- 4.3. Case Study 3: Comparison of Pharmacodynamics in Animals -- 4.4. Case Study 4: Integrating In Vitro Methodologies into -- Table 1 Percent of Subjects Reaching Evernimicin Preclinical Targets -- 5. CONCLUSIONS -- ACKNOWLEDGEMENTS -- REFERENCES -- 7 -- Formulation and Route of Administration-Influencing Drug Permeability and Absorption -- 1. ORAL DRUG DELIVERY -- 1.1. Anatomy and Physiology of the GI Tract -- 1.2. Factors Affecting the Oral Absorption -- 1.3. Experimental Models for Oral Transport Studies -- 1.4. Drug Delivery Systems for Oral Use -- 2. TRANSDERMAL DRUG DELIVERY -- 2.1. Structure of the Skin -- 2.2. Transport of Drug Molecules Across the Skin -- 2.3. Evaluation of Transdermal Drug Delivery Kinetics -- 3. NASAL DRUG DELIVERY -- 3.1. Nasal Anatomy and Physiology -- 3.2. Factors Affecting Nasal Drug Absorption -- 3.3. Models for Nasal Drug Absorption -- 3.4. Nasal Drug Delivery Systems -- 3.5. Absorption Promoters in Nasal Drug Delivery -- 4. PULMONARY DRUG DELIVERY -- 4.1. Anatomy and Physiology of Respiratory Tract -- 4.2. Factors Affecting Drug Deposition and Absorption via the Pulmonary Route. 4.3. Models for Assessing Systemic Drug Absorption After Pulmonary Delivery -- 4.4. Pulmonary Drug Delivery Systems and Devices -- 5. CONCLUSIONS AND IMPLICATIONS FOR PRECLINICAL DRUG DEVELOPMENT -- REFERENCES -- 8 -- Assessment of Pharmacokinetics and Drug Activity: Isolated Organ Systems and the Membrane Transporter Family -- 1. INTRODUCTION -- 2. OVERVIEW OF MEMBRANE TRANSPORTERS -- 2.1. ATP-Binding Cassette Transporters -- Table 1 Summary of Membrane Transporters Involved in Drug Disposition -- Table 2 Substrates for Pgp -- 2.2. Organic Anion Transporters -- 2.3. Organic Cation Transporters -- 2.4. Peptide Transporters -- 2.5. Nucleoside Transporters -- 3. EXPERIMENTAL METHODS USED TO STUDY MEMBRANE DRUG TRANSPORT -- 3.1. Pharmaceutical Molecular Biology -- Table 3 In Vitro Methods for Studying Drug Transport -- Table 4 Survey of Cell Lines/Transfected Cell Lines Used To Study Drug Transport -- 3.2. Membrane Vesicles -- 3.3. Isolated Perfused Organs -- 3.4. Whole Animal Models (Transgenic Animals and Mutant Strains) -- 4. HEPATOBILIARY TRANSPORT -- 4.1. Organic Cation Transport -- Table 5 Classification of Organic Cations: Hepatobiliary Transport -- Table 6 Summary of Studies Demonstrating Pgp-Mediated Biliary Excretion of -- 4.2. Organic Anion Transport -- Table 7 Substrates for MRP2 (cMOAT) -- 5. GASTROINTESTINAL TRANSPORT 5.1. Traditional View of Intestinal Absorption -- 5.2. Membrane Transporters Involved in GI Absorption -- Table 8 List of Substrates for Both Pgp and CYP3A4 -- 6. RENAL TRANSPORT 6.1. Overview of Renal Excretion -- 6.2. Organic Cation Transport -- Table 9 Substrates for Renal Tubular Transport Systems: Organic Cation Trans-porters -- 6.3. Organic Anion Transport -- Table 10 Substrates for Organic Anion Renal Tubular Transporters -- 6.4. Other Renal Transporters -- 7. CENTRAL NERVOUS SYSTEM TRANSPORT. 7.1. Transport Systems for CNS Uptake -- 7.2. Transport Mechanisms for CNS Efflux -- Table 11 Summary of Transport Mechanisms for Uptake and Efflux Across BBB -- Table 12 List of Compounds Transported at BBB via Pgp and other Transport -- 8. IMPACT OF MEMBRANE TRANSPORTERS ON OTHER ORGANS AND TISSUES -- 9. IMPLICATIONS FOR PRECLINICAL DRUG DEVELOPMENT -- 9.1. Emerging Areas of Importance -- 9.2. High-Throughput Screening for Transporter Affinity -- 9.3. Targeted Drug Delivery -- 9.4. Clinical Implications of Membrane Transporters -- REFERENCES -- 9 -- Alternate Methods for Assessing Absorption, Metabolism, and Routes of Elimination -- 1. INTRODUCTION -- 2. THE EVOLUTION OF DRUG DISCOVERY AND ITS EFFECT ON PRECLINICAL DEVELOPMENT -- 3. LEAD SELECTION AND OPTIMIZATION VIA PHARMACEUTICAL PROFILING -- 3.1. Solution Properties -- Table 1 Measurement of the Kinetic Solubility of Marketed -- Table 2 Plasma Protein Binding of Existing Medications: A Limited Comparison -- 3.2. Intestinal Permeability and Absorption -- Table 3 Ranking of Existing Medicines for Transcellular -- Table 4 -- 3.3. Hepatic Metabolism -- Table 5 Inhibition of Cytochrome P450 Enzymes by Reference Compounds -- Table 6 The Biopharmaceutics Classification System -- 3.4. Cellular Toxicity -- 4. CONCLUSION -- ACKNOWLEDGEMENT -- REFERENCES -- 10 -- Toxicity Evaluations: ICH Guidelines and Current Practice -- 1. CHAPTER OVERVIEW -- 2. INTRODUCTION -- 2.1. ICH Topics -- 2.2. Parties to ICH -- Table 1 Four Categories of ICH Topics -- 2.3. Steps in the Process of Harmonization in the ICH Process -- 3. ICH NON-CLINICAL (PRECLINICAL) TOXICITY GUIDELINES -- Table 2 ICH Non-clinical Toxicity Testing Guidelines -- 3.1. Single-Dose Toxicity Guidance (ICH Topic S4) -- 3.2. Repeat-Dose Toxicity Guidances -- Table 3 Duration of Repeated-Dose Toxicity Studies to Support Phase I and II.
520			_aThis reference discusses in detail the broad realm of preclinical drug development. Topics range from assessment of pharmacology and toxicology through the regulatory expectations that support clinical trials. Providing chapters on pharmacokinetics, modeling and simulation, formulation and routes of administration, toxicity evaluations, the assessment of drug absorption and metabolism, and interspecies scaling, this guide is a fundamental resource for medicinal chemists, biologists, and other specialists in the drug development sciences.
530			_aAlso available online
650		0	_aDrug development
650	1	2	_aDrug Evaluation, Preclinical _xmethods
650	2	2	_aDrug Industry _xmethods
700	1		_aRogge, Mark C _eauthor
700	1		_aTaft, David R _eauthor
942			_2ddc _cBK