GlossaryPharmacokineticsCmin
Pharmacokinetics

Cmin

Also known as: trough concentration · minimum plasma concentration

Cmin is the lowest concentration of a drug in your blood during a dosing interval, usually reached just before the next dose (the trough).

Cmin (minimum concentration) is the bottom of the concentration-time curve within one dosing interval at steady state. FDA guidance lists it separately from Ctrough, the concentration measured at the end of the dosing interval, right before the next dose. The two are often close, but they are defined differently, so check which one a study reports before comparing numbers.

The gap between peak and trough is summarized by fluctuation, (Cmax − Cmin) / Cavg, and swing, (Cmax − Cmin) / Cmin, where Cavg is the average concentration over the interval. How deep the trough goes depends on the dosing interval compared with the half-life. Dose at an interval much shorter than the half-life and the trough stays close to the peak; dose at an interval several times longer and levels fall far before the next dose.

Why it matters

Trough levels show whether exposure is sustained across the whole interval or rises and falls sharply. In approved long-acting peptides, the dosing interval is about one to two half-lives: semaglutide has an elimination half-life of about 1 week and is dosed once weekly, and liraglutide has a half-life of about 13 hours and is dosed once daily.

Ctrough is also how steady state is checked. FDA guidance asks for Ctrough over at least two dosing intervals to judge whether steady state has been reached, so if you are reading a study, a stable trough across consecutive doses is the sign that levels have stopped climbing. For research peptides without human pharmacokinetic studies, statements that levels 'stay elevated' between doses have no measured troughs behind them.

How to estimate it

  1. Get a sourced half-life (t½) and your dosing interval (τ) in the same units.
  2. Compute τ / t½.
  3. In a simple model with fast absorption, the steady-state peak-to-trough ratio is 2^(τ / t½); the trough is the peak divided by that ratio.
  4. Slow SubQ absorption spreads each dose out over time, so real peak-to-trough ratios are usually smaller than this estimate.

Peak-to-trough ratio ≈ 2^(τ / t½) (one-compartment model, rapid absorption)

Worked example

Semaglutide, t½ about 168 hours, dosed every 168 hours: 2^(168/168) = 2^1 = 2, so in this model the trough is about half the peak. Liraglutide, t½ about 13 hours, dosed every 24 hours: 24 / 13 = 1.85 and 2^1.85 ≈ 3.6, so the trough is about 1 / 3.6 ≈ 28% of the peak. Both drugs absorb slowly (liraglutide peaks 8 to 12 hours after a dose, semaglutide 1 to 3 days), so actual swings are smaller than these figures.

Common mistakes

  • Treating Cmin (lowest level in the interval) and Ctrough (level just before the next dose) as the same number when comparing studies.
  • Judging troughs before steady state; early troughs are lower than they will be once levels stop accumulating.
  • Assuming a trough below some number means 'no effect' when no source has established an effective concentration for that compound.
  • Estimating troughs from a half-life that was measured in animals or quoted without a source.
  • Forgetting that a late or missed dose lowers the trough for that interval.

Sources

  1. GuidelineBioavailability Studies Submitted in NDAs or INDs — General Considerations: Guidance for Industry. U.S. Food and Drug Administration (CDER), 2022.
  2. Prescribing informationOZEMPIC (semaglutide) injection, for subcutaneous use: Prescribing Information. Novo Nordisk (FDA-approved labeling), 2026.
  3. Prescribing informationVICTOZA (liraglutide) injection, for subcutaneous use: Prescribing Information. Novo Nordisk (FDA-approved labeling), 2025.

Page updated . How we grade evidence: methodology.

Related Terms

Cmax

Cmax is the highest concentration a drug reaches in your blood after a dose; Tmax is how long after the dose that peak occurs.

Steady State

Steady state is the point in repeated dosing where the drug eliminated each interval equals the drug taken in, so levels stop climbing.

Half-Life

Half-life (t½) is the time it takes for the concentration of a drug in your blood plasma to fall by half.

AUC (Area Under Curve)

AUC (area under the curve) is your total exposure to a drug over time: the area under its blood concentration-time curve.

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