Bioavailability

Bioavailability is the fraction of an administered dose that reaches the systemic circulation in an unchanged form. It is the quantitative endpoint of the absorption phase, combining how completely a drug is absorbed with how much survives first-pass metabolism, and it is the basis on which exposures from different routes and products are compared.

Definition

Bioavailability (F) is the fraction of an administered dose of unchanged drug that reaches the systemic circulation; absolute bioavailability compares a route against an intravenous reference (defined as F = 1), while relative bioavailability compares one non-intravenous product or route against another.

Scope

This topic defines bioavailability, distinguishes absolute from relative bioavailability, and describes how it is estimated from drug exposure. It treats bioavailability as a pharmacokinetic measure and supporting concept for bioequivalence; it does not give dosing or product-selection advice.

Key concepts

• Absolute bioavailability
• Relative bioavailability
• Area under the concentration-time curve (AUC)
• Intravenous reference (F = 1)
• Extent versus rate of absorption
• Interindividual variability in bioavailability
• Link to bioequivalence

Mechanisms

Bioavailability is the product of the fraction of dose absorbed and the fraction that escapes first-pass metabolism in the gut wall and liver. It is estimated by comparing systemic exposure — most commonly the area under the plasma concentration-time curve (AUC) — after the route of interest with that after an intravenous dose (for absolute bioavailability) or after a reference product (for relative bioavailability), with appropriate adjustment for dose. Because the extent of absorption varies between people, bioavailability itself can be a source of interindividual variability in exposure, as Hellriegel and colleagues showed.

Clinical relevance

Bioavailability quantifies how much of a dose reaches the circulation and so underpins comparisons between routes and between products, including the logic of bioequivalence assessment. This entry explains the measure for evidence appraisal and education; it does not recommend doses, products, or substitutions for any individual.

Evidence & guidelines

The Biopharmaceutics Classification System of Amidon and colleagues links bioavailability to a drug's solubility and intestinal permeability and informs regulatory frameworks for oral products. Observational pharmacokinetic work such as Hellriegel and colleagues relates variability in bioavailability to the extent of absorption, and standard texts such as Rowland and Tozer define the absolute and relative measures used here.

History

Bioavailability became a defined, measurable quantity as biopharmaceutics and clinical pharmacokinetics developed in the second half of the twentieth century and exposure-based comparisons replaced cruder measures of absorption. Amidon and colleagues' 1995 Biopharmaceutics Classification System tied bioavailability to solubility and permeability, and the concept became central to bioequivalence and the regulation of generic medicines.

Key figures

• Gordon L. Amidon
• Malcolm Rowland
• Thomas N. Tozer
• Edward T. Hellriegel

Seminal works

• amidon-1995
• hellriegel-1996

Frequently asked questions

What is the difference between absolute and relative bioavailability?

Absolute bioavailability compares a route or product against an intravenous dose (taken as 100%), whereas relative bioavailability compares one non-intravenous product or route against another reference product.

How is bioavailability measured?

It is usually estimated from systemic drug exposure — the area under the plasma concentration-time curve — comparing the route of interest with an intravenous or reference dose after accounting for the dose given.