Peptide Half-Life Explained

Half-life (t½) is the time required for the concentration of a peptide in the blood to fall to 50% of its peak level. If a peptide has a half-life of 30 minutes, then 30 minutes after administration, 50% of the dose remains; after 60 minutes (two half-lives), 25% remains; after 90 minutes (three half-lives), 12.5% remains.

Half-life determines how long a peptide remains active and how frequently it must be dosed.

Natural peptides are often rapidly degraded by proteolytic enzymes in the blood and tissues, resulting in short half-lives (minutes to hours). Engineered peptides designed to resist enzymatic degradation have longer half-lives. PEGylation (attaching polyethylene glycol polymer), D-amino acid incorporation, and other modifications extend half-life.

A longer half-life allows less frequent dosing, improving patient convenience.

Peptides with short half-lives must be dosed frequently (daily or more often) to maintain therapeutic concentrations. Peptides with long half-lives require less frequent dosing (weekly or monthly). The half-life also affects how long it takes to reach steady-state (approximately 5 half-lives) and how long it takes to clear the peptide after stopping it.

Insulin has a half-life of about 5 minutes; it must be dosed multiple times daily. Semaglutide (a GLP-1 agonist) has a half-life of about 7 days; it is dosed once weekly. CJC-1295 (a GHRH analogue) has an extended half-life and is dosed less frequently than natural GHRH, which has a half-life of just minutes.