Drug exposure (AUC, Cmax, Ctrough)
Drug exposure is how much drug is in the body over time, summarized by AUC, Cmax, Ctrough or an average concentration. The same dose gives different exposure in different patients.
Frequently asked questions
What is the difference between dose and exposure?
The dose is the amount administered. The exposure is the concentration–time profile that results, summarized by metrics such as AUC, Cmax and Ctrough. Patients who receive the same dose can have different exposure because clearance and volume of distribution differ.
Which exposure metric should be used?
It depends on the question: Cmax for a peak-related event, Ctrough or time above a threshold for a sustained target effect, and AUC for cumulative effects. Choose the metric and the time window before analyzing the outcome.
Is exposure the same as the concentration at the target?
Not necessarily. Exposure is usually measured in plasma or serum. The unbound concentration and the concentration at the site of action can differ from it.
Drug exposure is a measure of how much drug is present in the body over time, usually summarized from concentrations as AUC, Cmax, Ctrough or an average concentration. The dose is the amount given; the exposure is what results, and it differs between patients who receive the same dose.
Definition
- Dose: the amount administered, for example 200 mg or 2 mg/kg.
- Exposure: the concentration–time profile that follows, and the metrics that summarize it: AUC for cumulative exposure, Cmax for the peak, Ctrough for the lowest concentration within an interval, and the average concentration.
Exposure is usually measured in plasma or serum. The concentration at the site of action, and the unbound fraction, may differ from it; see unbound drug concentration.
Why it differs between patients
With the same dose, exposure depends on clearance and volume of distribution, and so on body weight, organ function, age, genetics, disease and co-medications (drug interactions). For an oral drug, absorption adds variability. This is why population PK models relate exposure, not only dose, to covariates.
How it is used
- Exposure–response analysis relates exposure to efficacy and safety outcomes, to choose a dose or to justify an adjustment (exposure–response).
- Metric choice: the metric should match the biology, for example a peak for a peak-related event and a trough for a sustained target effect (choosing an exposure metric).
- Safety margins: exposure in animals at the no-effect dose is compared with expected human exposure (exposure margins).
Common pitfalls
- Equating a higher dose with higher exposure in every patient; clearance differences can make a lower dose in one patient match a higher dose in another.
- Comparing exposure metrics from different time windows, such as the first dose and steady state, as if they were the same quantity.
- Reading an exposure–outcome association as causal when clearance and disease severity are linked (confounding).