Rogge / Taft Preclinical Drug Development, Second Edition

2. Auflage 2013
ISBN: 978-1-4200-8473-3
Verlag: Taylor & Francis
Format: PDF
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 376 Seiten

Reihe: Drugs and the Pharmaceutical Sciences

Preclinical Drug Development, Second Edition discusses the broad realm of preclinical drug development, ranging from assessment of pharmacology and toxicology to the industry trends and regulatory expectations and requirements that support clinical trials. This guide is a fundamental resource for medicinal chemists, biologists, and other specialists in the drug development sciences. The newly revised Second Edition includes:

Zielgruppe

Medicinal chemists, biologists, pharmacologists, and toxicologists in drug development; and academic faculty and students

Autoren/Hrsg.

Rogge, Mark

Taft, David R.

Fachgebiete

• Medizin | Veterinärmedizin Medizin | Public Health | Pharmazie | Zahnmedizin Medizinische Fachgebiete Pharmakologie, Toxikologie

Inhaltsverzeichnis

1. The Scope of Preclinical Drug Development: An Introduction and Framework. 2. Lead Molecule Selection – Pharmaceutical and Toxicity Assessments. 1. Introduction. 2. The Evolution of Drug Discovery and Its Impact on Preclinical Development. 3. Lead Selection and Optimization via Pharmaceutical Pro?ling. 4. Screening via In Silico and In Vitro Toxicity Evaluations. 5.        Conclusion. References. 3. Interspecies Differences in Physiology and Pharmacology: Extrapolating Preclinical Data to Human Populations. 1. Overview. 2. Toxicology Tests: Points to Consider. 3. Toxicological Endpoints. 4. Factors that Can In?uence Study Results. 5. Interspecies Pharmacokinetic Differences. 6. Allometry. 7. Concluding Thoughts. References. 4. Pharmacokinetics/ADME of Small Molecules. 1. Introduction. 2. Pharmacokinetics: General Overview. 3. Mechanisms of Small Molecule Absorption. 4. Mechanisms of Small Molecule Distribution. 5. Mechanisms of Small Molecule Metabolism. 6. Mechanisms of Small Molecule Excretion. 7. Small Molecule ADME: Issues for Drug Development. 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. 3. Distribution of Protein Therapeutics. 4. Plasma Pharmacokinetics. 5. Protein Binding of Protein Therapeutics. 6. Interspecies Scaling. 7. Heterogeneity of Protein Therapeutics. 8. Chemical Modi?cations 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 Make Them? 3. What Conditions Are Necessary for the Preclinical Model to be Valid in Humans? 4. Case Studies. 5. Conclusions. References. 7. Formulation and Route of Administration—In?uencing Drug Permeability and Absorption. 1. Oral Drug Delivery. 2. Transdermal Drug Delivery. 3. Nasal Drug Delivery. 4. Pulmonary Drug Delivery. 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. 3. Experimental Methods Used to Study Membrane Drug Transport. 4. Hepatobiliary Transport. 5. Gastrointestinal Transport. 6. Renal Transport. 7. Central Nervous System Transport. 8. Impact of Membrane Transporters on Other Organs and Tissues. 9. Implications for Preclinical Drug Development. 9. Toxicity Evaluations: ICH Guidelines and Current Practice. 1. Chapter Overview. 2. Introduction. 3. ICH Non-Clinical (Preclinical) Toxicity Guidelines. 4. Additional Safety Topics and Guidelines. 5. Non-Clinical Development Program. 6. Conclusions. References. 10. Application of Pathology in Safety Assessment. 1. Introduction. 2. Technical Post-Mortem Procedures. 3. General Pathology. 4. Typical Non-Neoplastic Alterations Seen in Toxicity Studies. 5. Typical Neoplastic Changes Seen in Life-Time Bioassays. 6. Investigation of Unclear Pathological Findings. 7. Interpretation of Pathological Findings. 8. Reporting. 9. Conclusions. References. 11. Utilizing the Preclinical Database to Support Clinical Drug Development. 1. Utilizing the Preclinical Database to Select Human Dose. 2. Utilizing the Preclinical Database to Support the Ef?cacy Claim for Regulatory Approval. 3. Utilizing Preclinical Database to Address Safety Concerns. 4. Utilizing the Preclinical Database to Design In Vivo Metabolic Drug–Drug Interaction Studies. 5. Limitations and Predictive Value of the Preclinical Database. 6. Conclusions. References.