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Bioavailability

Bioavailability

For medical students2 min readUpdated 2026-10-10

Bioavailability (denoted as $F$) is the fraction of an administered drug dose that successfully reaches the systemic circulation unchanged. For oral medications, this crucial pharmacokinetic parameter is always determined by comparing experimental blood levels to those achieved via a reference intravenous injection.

Main GoalTo assess the fraction of a drug that reaches the systemic circulation.
Test RouteOral administration (*per os*).
Reference RouteIntravenous injection (considered 100%).
Key ParameterAUC (Area Under the Curve).

Concept of Bioavailability

In clinical pharmacology, bioavailability provides an exact quantitative measure of how much active substance enters the bloodstream after administration. When evaluating the systemic circulation, we exclude the portion of the dose lost or unabsorbed along the way. To determine this value for tablets or capsules taken by mouth, a direct comparison with intravenous administration is required.

Experimental Determination

Oral bioavailability (per os) is always determined experimentally by comparing two routes of administration in the same subject.

The clinical experiment involves the following strict steps:

  1. Reference administration. The subject is first given the test drug intravenously (IV), which is considered the gold standard.
  2. Initial measurements. Blood samples are collected at strictly fixed time intervals to measure drug concentration, generating the IV concentration-time curve.
  3. Test administration. After a sufficient washout period, the exact same dose of the drug is given orally to the same subject.
  4. Secondary measurements. Blood samples are collected again in the same manner to generate the oral concentration-time curve.

Key Evaluation Parameter (AUC)

Pharmacologists analyze concentration-time curves derived from the measurements. The most critical metric extracted from these graphs is the area under the curve.

Internationally, this parameter is designated as AUC (Area Under the Curve). The plasma concentration-versus-time AUC provides an objective measure of the total systemic drug exposure over the entire observation period.

Calculating Bioavailability

A simple mathematical formula converts graphical data into specific numerical values. Because intravenous administration introduces the drug directly into the systemic circulation with no pre-systemic loss, its AUC is considered the absolute maximum (100%).

Calculation formula: $$F = \frac{AUC_{oral}}{AUC_{IV}} \times 100\%$$

Thus, bioavailability is the ratio of the AUC following oral administration to the AUC following intravenous administration.

Mnemonic

The formula is easy to remember logically: divide what is tested ($AUC_{oral}$) by the absolute ideal ($AUC_{IV}$), and multiply the result by 100%.

Frequently asked questions

What factors reduce the bioavailability of an orally administered drug?

Oral bioavailability is reduced due to gastrointestinal and hepatic barriers. Key factors include:

  • Physicochemical and enzymatic factors in the GI tract — degradation by gastric hydrochloric acid, inactivation by digestive enzymes, and incomplete absorption.
  • Intestinal wall metabolism — biotransformation within enterocytes (e.g., Levodopa).
  • Active transport — efflux of substrates from enterocytes back into the intestinal lumen via P-glycoprotein.
  • Pre-systemic elimination — extensive first-pass metabolism in the liver.
  • Increased GI motility — reduced contact time with the mucosal absorptive surface.

Additionally, food intake can significantly alter the bioavailability of certain drugs.

What is pre-systemic metabolism and how does it affect bioavailability?

Pre-systemic metabolism (pre-systemic elimination or first-pass effect) refers to the loss of a drug before it reaches the systemic circulation following oral administration. As a result, a smaller fraction of the drug reaches the systemic circulation compared to the amount absorbed from the intestinal lumen. First-pass elimination can occur via:

  • Hepatic metabolism as blood passes through the portal circulation.
  • Intestinal wall metabolism involving CYP3A4 enzymes, alongside P-glycoprotein-mediated efflux back into the gut lumen.

An intense first-pass effect reduces bioavailability; for some drugs, this renders oral administration ineffective or necessitates significantly higher oral doses.

Why is intravenous administration used as the reference?

With intravenous administration, the entire dose enters the systemic circulation immediately and without losses, making it the 100% reference standard.

What does AUC stand for?

AUC stands for Area Under the Curve on a graph depicting drug concentration versus time.

Why is the same subject used in the experiment?

Both the test (oral) and reference (IV) administrations are performed on the same subject to eliminate inter-individual pharmacokinetic variability.

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