CHAPTER 8: ADME Properties of Peptide Therapeutics in Drug Discovery and Development

Through the years, the collective knowledge gained in the science of drug metabolism and pharmacokinetics (DMPK) has led to a basic strategy of optimizing the pharmacokinetics of small molecules that, at its core, includes understanding the mechanism of clearance of a molecule, identifying areas susceptible to metabolism and understanding factors that limit bioavailability. As evidence of the benefits of this approach, adoption of DMPK input early in the drug discovery process has greatly reduced the rate of attrition of clinical candidates due to poor human pharmacokinetics. A similar approach can be taken with peptide therapeutics; however, the level of understanding of the absorption, distribution, metabolism and elimination (ADME) properties of peptide therapeutics has not matured to the extent that it has for small molecules.