Measuring Bioavailability: AUC, Cmax and the Two Questions

Reading the concentration curve

Give a dose, then draw blood at intervals and measure drug concentration. Plot concentration against time and you get the familiar rise-and-fall curve. Three numbers summarise it. The peak height is Cmax, the highest concentration reached. The time at which that peak occurs is Tmax. And the area under the whole curve is the AUC. Together they answer the two questions of bioavailability: how much got in, and how fast.

AUC measures the extent of absorption — the total exposure, how much drug the body actually saw over time. Cmax and Tmax together describe the rate of absorption — a fast-absorbing product peaks high and early, a slow one peaks lower and later. Crucially, two products can have the same AUC but very different Cmax and Tmax: the same total amount delivered, but at different speeds. That distinction will matter enormously when we compare products.

Absolute vs relative bioavailability

Bioavailability is always a comparison. Absolute bioavailability (F) compares your product to an intravenous dose — the gold standard where 100% reaches the blood by definition. It tells you what fraction of an oral dose truly survives the gut and the first-pass effect. Relative bioavailability compares one non-intravenous product to another — say a new tablet versus an existing solution, or a generic versus the brand. There is no IV reference, so the answer is a ratio, not an absolute fraction.

1. Give the test product orally and measure its AUC; normalise by the oral dose.
2. For absolute F, give an intravenous dose to the same subjects on another occasion and measure its AUC; normalise by the IV dose.
3. Divide the dose-corrected oral AUC by the dose-corrected IV AUC; the result is F, between 0 and 1.
4. For relative bioavailability, swap the IV reference for the comparator product and skip the IV step entirely.

A worked bioavailability calculation

The arithmetic is one formula. Always correct for dose, because the oral and IV doses are usually different. Then it is a clean ratio of areas.

Absolute bioavailability F

  F = (AUC_oral / Dose_oral) / (AUC_iv / Dose_iv)

Data:
  AUC_oral = 18 mg.h/L     Dose_oral = 100 mg
  AUC_iv   = 30 mg.h/L     Dose_iv  = 50 mg

  F = (18 / 100) / (30 / 50)
    = 0.18 / 0.60
    = 0.30   ->  30% of the oral dose reaches the circulation

Relative bioavailability (test vs reference, same dose)

  F_rel = AUC_test / AUC_reference
        = 22 / 20 = 1.10  ->  test product gives 10% more exposure