The half-life (t½) of a compound is the time required for its plasma concentration to decline to half of a given starting value. For a compound following first-order elimination kinetics, t½ is a constant related to the elimination rate constant kₑ by the relationship t½ = ln(2) / kₑ ≈ 0.693 / kₑ.
Half-life determines the dosing interval required to maintain a steady-state plasma concentration and the time to reach and depart from that steady state (approximately four to five half-lives). Native peptides typically show very short half-lives (minutes to a few hours) due to rapid proteolytic degradation and renal clearance; modifications such as albumin-binding lipid tails or pegylation extend it substantially.
Half-life is one of the two variables (with bioavailability) that define a peptide's dosing profile and is central to any preclinical pharmacokinetic characterisation.
