Peptide half-lives

Why half-life drives dosing frequency

Elimination half-life is the time it takes for the concentration of a substance in blood to fall by half. It is the single number that most determines how often a drug has to be given, because it sets two things at once: how quickly a dose disappears, and how much of the previous dose is still present when the next one arrives. Give a substance at intervals much longer than its half-life and each dose behaves as an isolated spike. Give it at intervals shorter than its half-life and concentrations accumulate until elimination catches up with input — a steady state that arrives, as a rule of thumb, after four to five half-lives.

The range in the table above spans four orders of magnitude, from minutes to a week, and that spread is the whole reason peptide dosing schedules look so different from one another. A compound cleared in minutes cannot hold a concentration between doses at all; whatever effect it has is a pulse, and the biology has to be the kind that responds to pulses. A compound with a half-life measured in days can be given weekly and still be present continuously, which is why the long-acting incretins are weekly drugs and why it takes over a month for them to reach steady state — and roughly as long to wash out after stopping.

Long half-lives are engineered, not accidental. Native peptides are cleared very fast, and the ones at the bottom of this table are close to their natural behaviour. The ones at the top have been modified to resist that clearance — most often by attaching a fatty-acid chain that binds serum albumin, so the molecule circulates bound and is released slowly, or by fusing it to a larger carrier protein. The same molecular family can therefore appear at both ends of this table depending on what was done to it.

These values are not interchangeable

A half-life is a measurement of a specific product, given a specific way, in a specific population — not a property of a molecule. That is why the route column exists, and why comparing across rows is hazardous even when the numbers look comparable.

Route matters most. Given intravenously, a substance is fully in circulation immediately and the measured half-life reflects elimination alone. Given subcutaneously, it has to be absorbed from the injection site first, and when absorption is slower than elimination the apparent half-life is really a measure of how slowly the depot empties. The number rises, sometimes several-fold, without anything about the molecule’s clearance having changed. Oral, intranasal and implanted formulations each shift it again — an implant can hold a release profile for months around a molecule whose circulating half-life is a few hours.

Several other caveats apply to every row. Values are typically reported in healthy adults, and renal or hepatic impairment can change them substantially. Ranges reflect real between-person variation, not measurement sloppiness. And half-life describes how long a substance is present, not how long it acts: effects driven by receptor occupancy, downstream gene expression, or tissue remodelling can outlast circulating drug by a wide margin, and effects requiring a concentration threshold can stop well before it is cleared. Duration of effect and duration of exposure are different quantities that happen to share a unit.

To see how a stated half-life translates into an accumulation curve, the half-life plotter prefills from these published values and plots concentration over repeated intervals. It is a visualisation of the arithmetic above, not a dosing recommendation — this page and that tool are educational and non-prescriptive throughout. See the medical disclaimer, and the dosing concepts guides for how these ideas are discussed per compound.