Cytochrome P450: In Vitro Methods and Protocols

Chapter provides background information useful in fully understanding how and why cytochrome P450 (CYP) in vitro methods and protocols are important in a modern drug discovery pipeline. We describe the organizational structure and the research activities within a typical pharmaceutical drug discovery and development company. The types of drug metabolism and pharmacokinetics (DMPK) and its drug disposition (ADME) properties, including in silico computational methods, in vitro ADME tests, and in vivo whole-animal models, are discussed and how these assays are being developed and applied to rational drug design. We discuss the interrelationship between drug physiology and pharmacology and how this interplay is used to develop DMPK assays. We suggest assay strategies for utilizing CYP in vitro methods and protocols, and finally, we discuss the future outlook for DMPK approaches in drug discovery. Chapter 2 provides comprehensive information concerning CYP enzymes and their related metabolism properties on xenobiotics, while Chapters 3 – 22 provide detailed CYP and non-CYP in vitro methods and protocols that can be easily established in a drug discovery pipeline.