Impact of Intrinsic and Extrinsic Factors on the Pharmacokinetics of Peptides: When Is the Assessment of Certain Factors Warranted?

Abstract

Peptides are short chains of 2 to 50 amino acids (molecular weight of less than 10 kDa) linked together by peptide bonds. As therapeutic agents, peptides are of interest because the body naturally produces many different peptides. Short-chain peptides have many advantages as compared with long-chain peptides (e.g., low toxicity). The first peptide corticotropin was approved in 1952 for multiple inflammatory diseases and West syndrome. Since then, more than 60 peptides have been approved by the FDA. Pharmacokinetics (PK) is widely used in modern-day drug development for designing a safe and efficacious dose to treat a wide variety of diseases. There are, however, several factors termed as “intrinsic” or “extrinsic” which can influence the PK of a drug, and as a result, one has to adjust the dose in a patient population. These intrinsic and extrinsic factors can be described as age, gender, disease states such as renal and hepatic impairment, drug–drug interaction, food, smoking, and alcohol consumption. It is well known that these intrinsic and extrinsic factors can have a substantial impact on the PK of small molecules, but for macromolecules, the impact of these factors is not well established. This review summarizes the impact of intrinsic and extrinsic factors on the PK of peptides.