Steady state in repeated dosing
At steady state the amount of drug entering the body per interval equals the amount leaving it, so the concentration profile repeats from dose to dose. Summary measures such as Ctrough,ss and Cavg,ss are taken at this point.
Definition
With repeated dosing, the drug accumulates until the amount entering the body in one dosing interval equals the amount eliminated in it. From then on, the concentration–time profile repeats from one interval to the next. This is steady state.
Time to steady state
For linear PK it is reached after about four to five half-lives, whatever the dose. Drugs with half-lives of weeks therefore take months.
Steady-state measures
- Cmax,ss: the peak within a steady-state interval (Cmax).
- Ctrough,ss (Cmin,ss): the lowest concentration (Ctrough).
- Cavg,ss: the average concentration, the dose rate divided by clearance (AUC).
On this site
The anti-PD-1 analysis evaluates the first dosing interval starting on or after day 364, to be at steady state, and the tarlatamab analysis compares regimens by their steady-state average, peak and trough.
Frequently asked questions
Why are regimens compared at steady state?
Because the profile no longer changes from dose to dose, so Cmax,ss, Ctrough,ss and Cavg,ss describe the long-term exposure that a regimen delivers.
Does a higher dose reach steady state sooner?
No. For linear PK the time to steady state depends on the half-life, not on the dose.