Ctrough (trough concentration)
Ctrough is the drug concentration measured just before the next dose, the lowest level within a dosing interval at steady state. It is used to compare dosing regimens, but a trough alone does not describe the whole exposure.
Definition
Ctrough (trough concentration) is the drug concentration measured immediately before the next dose is given. At steady state it is written Ctrough,ss (or Cmin,ss): the lowest concentration within a dosing interval, reached when the previous dose has been eliminated as far as it will be before the next one.
How it differs from other exposure measures
- Cmax: the highest concentration in the interval (the peak).
- Cavg: the average concentration over the interval, which equals the dose rate divided by clearance at steady state for linear PK.
- Cmin: the minimum concentration observed in the interval. It is usually close to Ctrough; Ctrough is defined as the pre-dose sample, Cmin as the lowest value.
- AUC: the area under the concentration–time curve over the interval.
Why the dosing interval matters
If the interval is lengthened while the average exposure is kept the same, the peak rises and the trough falls. In the simulation of anti-PD-1 regimens, 400 mg every 6 weeks of pembrolizumab had nearly the same average concentration as 200 mg every 3 weeks, but a lower trough. Whether the trough or the average concentration is the right criterion depends on the exposure–response relationship, which that analysis does not settle. The tarlatamab analysis shows the same direction for an interval change at constant dose intensity.
Related terms
Dosing interval notation (Q2W, Q3W, Q4W) and fixed versus weight-based dosing.
Frequently asked questions
Are Ctrough and Cmin the same?
Usually nearly. Ctrough is the concentration measured just before the next dose, and Cmin is the lowest concentration in the interval. After an intravenous dose with a steadily falling concentration they coincide.
Why does a longer dosing interval lower the trough at the same average exposure?
The same total dose is spread over a longer time, so the concentration falls further before the next dose and rises higher after it. The average is unchanged, but the trough is lower and the peak is higher.
Is a low Ctrough always a problem?
Not by itself. Whether a trough below a reference value matters depends on the exposure–response relationship of the drug, which has to be established separately; a trough comparison shows exposure, not effect.