Preclinical Drug Development is an essential resource for medicinal chemists, biologists, and any specialist involved in the drug development sciences.
Discussing the A to Z’s of preclinical drug development, this text includes the latest industry trends and regulatory expectations and requirements.
Recent cases studies and drug development simulation methods are included to illustrate emerging techniques and strategies.
Contents
1. The Scope of Preclinical Drug Development: An Introduction and Framework
2. Lead Molecule Selection – Pharmaceutical and Toxicity Assessments
- The Evolution of Drug Discovery and Its Impact on Preclinical Development
- Lead Selection and Optimization via Pharmaceutical Profiling
- Screening via In Silico and In Vitro Toxicity Evaluations
3. Interspecies Differences in Physiology and Pharmacology: Extrapolating Preclinical Data to Human Populations
- Toxicology Tests: Points to Consider
- Toxicological Endpoints
- Factors that Can Influence Study Results
- Interspecies Pharmacokinetic Differences
- Allometry
4. Pharmacokinetics/ADME of Small Molecules
- Pharmacokinetics: General Overview
- Mechanisms of Small Molecule Absorption
- Mechanisms of Small Molecule Distribution
- Mechanisms of Small Molecule Metabolism
- Mechanisms of Small Molecule Excretion
- Small Molecule ADME: Issues for Drug Development
- Pharmacokinetic/Pharmacodynamic (PK/PD) Modeling of Preclinical Data
5. Pharmacokinetics/ADME of Large Molecules
- Clearance Mechanisms of Protein Therapeutics
- Distribution of Protein Therapeutics
- Plasma Pharmacokinetics
- Protein Binding of Protein Therapeutics
- Interspecies Scaling
- Heterogeneity of Protein Therapeutics
- Chemical Modifications of Protein Therapeutics
- Immunogenicity
6. Preclinical Pharmacokinetic–Pharmacodynamic Modeling and Simulation in Drug Development
- What Is a Model and Why Do We Make Them?
- What Conditions Are Necessary for the Preclinical Model to be Valid in Humans?
- Case Studies
7. Formulation and Route of Administration—Influencing Drug Permeability and Absorption
- Oral Drug Delivery
- Transdermal Drug Delivery
- Nasal Drug Delivery
- Pulmonary Drug Delivery
8. Assessment of Pharmacokinetics and Drug Activity: Isolated Organ Systems and the Membrane Transporter Family
- Overview of Membrane Transporters
- Experimental Methods Used to Study Membrane Drug Transport
- Hepatobiliary Transport
- Gastrointestinal Transport
- Renal Transport
- Central Nervous System Transport
- Impact of Membrane Transporters on Other Organs and Tissues
- Implications for Preclinical Drug Development References
9. Toxicity Evaluations: ICH Guidelines and Current Practice
- ICH Non-Clinical (Preclinical) Toxicity Guidelines
- Additional Safety Topics and Guidelines
- Non-Clinical Development Program
10. Application of Pathology in Safety Assessment
- Technical Post-Mortem Procedures
- General Pathology
- Typical Non-Neoplastic Alterations Seen in Toxicity Studies
- Typical Neoplastic Changes Seen in Life-Time Bioassays
- Investigation of Unclear Pathological Findings
- Interpretation of Pathological Findings
11. Utilizing the Preclinical Database to Support Clinical Drug Development
- Utilizing the Preclinical Database to Select Human Dose
- Utilizing the Preclinical Database to Support the Efficacy Claim for Regulatory Approval
- Utilizing Preclinical Database to Address Safety Concerns
- Utilizing the Preclinical Database to Design In Vivo Metabolic Drug–Drug Interaction Studies
- Limitations and Predictive Value of the Preclinical Database
Index
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