This one-stop reference systematically covers key aspects in early drug development that are directly relevant to the discovery phase and are required for first-in-human studies. Its broad scope brings together critical knowledge from many disciplines, ranging from process technology to pharmacology to intellectual property issues. After introducing the overall early development workflow, the critical steps of early drug development are described in a sequential and enabling order: the availability of the drug substance and that of the drug product, the prediction of pharmacokinetics and -dynamics, as well as that of drug safety. The final section focuses on intellectual property aspects during early clinical development. The emphasis throughout is on recent case studies to exemplify salient points, resulting in an abundance of practice-oriented information that is usually not available from other sources. Aimed at medicinal chemists in industry as well as academia, this invaluable reference enables readers to understand and navigate the challenges in developing clinical candidate molecules that can be successfully used in phase one clinical trials.
Autorentext
100 international patents, peer-reviewed publications and book chapters.
Inhalt
Introduction to Early Drug Development PART I: Drug Substance Early Phase API Process Development Overview The Discovery-Development API Transition API Cost of Goods: Discovery to Early Development New technologies in Process Development Case Study: Vortioxetine and Early Drug Development Considerations at the Interface of R&D Case study: Development of a Practical Synthesis of 4'-Azido-2'beta-Methyl-2'-Desoxycytosine and Its Prodrugs as HCV Chemotherapeutic Agents PART II: Drug Product Solubility, Permeability, and their Interplay Drug Products: Solid-State Properties Salt and Cocrystal Screening Particle Size Reduction-From Microsizing to Nanosizing Drug Product Formulation A Practical Guide for the Preparation of Drug Nanosuspensions for Preclinical and Early Drug Development Studies PART III: Pharmacokinetics and Pharmacodynamics Integration of Pharmacokinetic and Pharmacodynamic Reasoning and Its Importance in Early Drug Development Prediction of Human Pharmacokinetics and Pharmacodynamics Translational Modeling and Simulation for Molecularly Targeted Small Molecule Anticancer Agents: Case Studies of Multiple Tyrosine Kinase Inhibitors, Crizotinib and Lorlatinib Informing Decisions in Discovery and Early Development Research Through Quantitative and Translational Modeling PART IV: Toxicology Pre-clinical Toxicology Evaluation Non-clinical Safety Pharmacology Predictive Computational Toxicology Addressing Genotoxicity Risk: A PDE10A Inhibitor Case Study The Integrated Optimisation of Safety and DMPK Properties Enabling Preclinical Development: A Case History with S1P1 Agonists From TRAIL to ONC201: Case Study on the Safety Benefit of Developing Targeted Agents Against Cancer-Selective Pathways PART V: Intellectual Property Patent Law Relevant to Early Drug Development Patent Protection Strategy The Patent Landscape Viewed from Generic and Originator Perspectives Patent Considerations in Collaborative Drug Development