In Vitro and In Vivo Assessment of ADME and PK Properties During Lead Selection and Lead Optimization – Guidelines, Benchmarks and Rules of Thumb

Assessment of the pharmacological properties of small molecule chemical compounds is critical to the initial selection or identification of a chemical lead, and during the further lead optimization to elucidate the Structure-Activity Relationships (SAR) and Structure Property Relationships (SPR), and ultimately to select the compound(s) that will enter Investigational New Drug (IND)-enabling studies. While extensive discussion of how Absorption, Distribution, Metabolism, and Excretion (ADME) of compounds affects their ultimate pharmacokinetics (PK) is beyond the scope of this chapter, herein, we provide guidelines for ADME and PK assessments, benchmarks and practical “rules of thumb” for selecting compounds with sufficient PK to be viable efficacious drugs.