A Review on the Metabolism of 25 Peptide Drugs

Although peptide drugs make up only about 2% of all drugs approved by the United States Food and Drug Administration (FDA), they play important roles in the treatment of certain diseases where no small molecule drugs or therapeutic antibodies can fulfil. A primary reason for the strong preference of small molecules over peptides is the latter’s susceptibility to degradation by human proteases, resulting in very short systemic half-lives. To circumvent this, peptide chemists have resorted to introducing unnatural amino acids and chemical modifications to enhance their metabolic stabilities. Hence, understanding how peptide drugs are metabolized by the human body will help in the design of more stable peptide drugs. This review covers 25 FDA-approved peptide drugs up to 20 residues in length and details their metabolic and degradation pathways in the human body after administration.