Half-life (t½)
The half-life is the time for a drug concentration to fall by half during elimination. It sets how long a drug takes to reach steady state and to wash out, and links clearance with volume of distribution.
Definition
The half-life (t½) is the time it takes for the concentration to fall by half in the terminal phase. For a one-compartment model with first-order elimination, t½ = ln 2 × V / CL: a larger volume lengthens it and a larger clearance shortens it. With several compartments there are several half-lives, and the terminal half-life is the slowest one.
Why it matters
- Steady state: with repeated dosing of a drug with linear PK, steady state is reached after about four to five half-lives.
- Washout: the drug is nearly eliminated after the same number of half-lives.
- Interval choice: a dosing interval much shorter than the half-life accumulates, and one much longer gives large fluctuations between peak and trough.
On this site
Antibodies have half-lives of weeks, so exposure in the anti-PD-1 analysis was evaluated from week 52 on, to be at steady state. The tarlatamab analysis compares intervals at constant dose intensity, where the interval relative to the half-life decides how much the peak and trough move. See also steady state.
Frequently asked questions
How long does it take to reach steady state?
For linear PK, roughly four to five half-lives of repeated dosing.
Does a longer half-life mean a longer dosing interval is possible?
It makes it possible to keep the trough within range with a longer interval, but whether a longer interval is acceptable depends on the peak, the trough and the exposure–response relationship.