Oral Bioavailability of Peptide and Peptidomimetic Drugs: Amino Acids, Peptides and Proteins in Organic Chemistry: Protection Reactions, Medicinal Chemistry, Combinatorial Synthesis, Volume 4

Peptide oral drug delivery has long been a challenging interest. Remarkable advances in recombinant DNA technology and synthetic chemistry, together with the development of receptor-based screening procedures, allow for the large-scale production of structurally diverse peptides exhibiting a broad spectrum of pharmacological effects. However, the development of these peptides/peptide-like compounds into effective drugs, and especially orally administered drugs, has been restricted due to various limitations, such as transport barriers, intestinal and hepatic metabolism, chemical instability, and hepatic elimination mechanisms. Development of an effective oral delivery system for this class of compounds requires a thorough understanding of the various physicochemical, physiological, and dosage formrelated factors governing the rate and extent of absorption following oral administration. In this chapter, we review the various factors influencing the oral systemic availability of peptide and peptidomimetic compounds, the barriers that compromise their systemic absorption, and the different approaches that have been utilized to overcome these barriers.