Absolute bioavailability (F)

Calculate absolute bioavailability from the areas under the curve and doses of an extravascular and an intravenous administration.

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What is this for?

Absolute bioavailability is the fraction of an administered dose that reaches the systemic circulation intact, referenced against intravenous administration which is 100% by definition. Because the doses used in the two study arms usually differ, the AUC ratio must be dose-normalised.

How to use it

Enter the AUC and dose from the extravascular (usually oral) study arm.
Enter the AUC and dose from the intravenous arm.
The dose normalisation is applied automatically, so the two arms do not have to have used the same dose.

Worked example

A 500 mg oral dose gives an AUC of 32 mg·h/L; a 500 mg intravenous dose gives 40 mg·h/L. What is the absolute bioavailability?

Answer: 100 × (32/40) × (500/500) = 80%. One fifth of the oral dose does not reach the systemic circulation, lost to incomplete absorption and first-pass metabolism.

Clinical pearls & pitfalls

The dose-normalisation term is essential. Comparing raw AUCs from arms given different doses is a common error that produces a nonsensical F.
Absolute bioavailability requires an intravenous reference. Comparing two oral products gives relative bioavailability, which is what bioequivalence studies measure.
Low bioavailability is not necessarily a problem — it only matters if it is also variable. A drug that is reliably 20% bioavailable can be dosed accurately; one that varies between 20% and 60% cannot.
F is dimensionless because the units cancel. If your answer carries units, you have made an algebraic error.

Assumptions & limitations

Requires an intravenous formulation to exist, which is not always the case.
Assumes linear pharmacokinetics — that clearance is the same in both arms and independent of dose. For drugs with saturable first-pass metabolism this fails.
AUC must be extrapolated to infinity for the calculation to be valid. A truncated AUC underestimates the true value, and does so unequally between arms.

References

US Food and Drug Administration. Guidance for Industry: Bioavailability and Bioequivalence Studies Submitted in NDAs or INDs — General Considerations. link
Rowland M, Tozer TN. Clinical Pharmacokinetics and Pharmacodynamics. 4th ed. Lippincott Williams & Wilkins.