Fundamentals
What is peptide half-life?
Last reviewed 2026-11-08 · Sources cited for every value
The definition
Most drugs, including most peptides at therapeutic concentrations, are eliminated by first-order kinetics: the rate of elimination is proportional to the amount present. That gives an exponential decline with a constant half-life:
t½ = ln 2 × V / CL ≈ 0.693 × V / CL
where V is the volume of distribution and CL is clearance. A compound stays longer either because it is cleared slowly (small CL) or because it spreads into a large volume (large V).
Show chart data as a table
| Series | 1× t½ | 2× t½ | 3× t½ | 4× t½ | 5× t½ |
|---|---|---|---|---|---|
| Illustrative 1-hour half-life | 1 hours · 50% | 2 hours · 25% | 3 hours · 12.5% | 4 hours · 6.25% | 5 hours · 3.125% |
How half-life is measured
Step 1
Administer
A study gives a known amount by a defined route (intravenous gives the cleanest elimination data).
Step 2
Sample
Blood is drawn at planned times and the intact compound is measured, usually by LC-MS/MS or immunoassay.
Step 3
Fit
The log-concentration curve is fitted, by noncompartmental analysis or a compartmental or population model.
Step 4
Report
The slope of the terminal phase gives the half-life, reported with its population, route and variability.
Assays matter: a method that measures radiolabel or fragments can report a much longer “half-life” than one that measures the intact peptide. This site records which was measured and keeps them apart.
Types of half-life that are not interchangeable
| Term | What it describes |
|---|---|
| Plasma elimination half-life | Time for plasma concentration to halve during the elimination phase. |
| Terminal half-life | The slowest, final phase when decline is multi-phasic; often longer than the initial phase. |
| Apparent half-life | A decline limited by slow absorption (flip-flop kinetics), common after subcutaneous depots. |
| Effective half-life | Derived from accumulation at steady state with repeated administration. |
| Duration of biological activity | How long an effect persists; not a concentration measure at all. |
| In-vitro stability | Breakdown in blood, plasma or buffer in a tube; does not include clearance in the body. |
Why peptide half-lives vary so much
Minutes
Unmodified sequences like native GHRH analogues are cut by proteases and filtered by the kidneys: tesamorelin and sermorelin are reported at under a quarter of an hour.
Hours
Partial protection, such as liraglutide's C16 fatty acid, gives roughly half a day (about 13 hours).
Days
Strong albumin binding or Fc fusion slows clearance to days: tirzepatide and dulaglutide about 5 days, semaglutide about 1 week.
Frequently asked questions
Is half-life the same as how long a peptide lasts?
No. Half-life describes how fast plasma concentrations fall. How long a biological effect lasts can be much shorter or longer, depending on receptor binding, signalling and tissue exposure.
Why do natural peptides have such short half-lives?
Proteases in blood and tissue break down unmodified peptide sequences within minutes, and small peptides are filtered by the kidneys. Many long-acting medicines are engineered specifically to avoid both.
What is a terminal half-life?
When concentrations fall in several phases (fast distribution into tissues, then slower elimination), the terminal half-life describes the final, slowest phase. It can differ a lot from the initial decline.
What does “apparent” half-life mean?
After subcutaneous administration, slow absorption from the depot can be the rate-limiting step. The decline then reflects absorption rather than elimination, often called flip-flop kinetics, and the measured value is an apparent half-life.