Essence of bioavailability
In clinical pharmacology, bioavailability provides a precise quantitative assessment of how much active substance ends up in the blood after drug administration. When we speak of the systemic circulation, we exclude that fraction of the dose that may have been lost or unabsorbed along the way. To find this figure for tablets or capsules taken orally, a direct comparison with the situation where the drug is administered directly into a vein must be performed.
Method of experimental determination
Bioavailability upon oral administration (taking by mouth, or per os) is always determined experimentally. It is based on comparing two ways of delivering the substance into the body of the same individual.
The clinical experiment includes the following rigorous steps:
- Reference administration. First, the selected patient is administered the test drug intravenously (IV). This route is considered ideal.
- Primary measurements. At strictly fixed time intervals, blood samples are taken from the patient and the drug concentration is measured. Based on these points, the first curve for intravenous administration is plotted.
- Test administration. After a necessary time interval, the exact same patient is given the exact same dose of the same drug, but this time orally.
- Secondary measurements. Again, similarly to the first step, the change in concentration over time is measured, and the second curve — for oral administration — is plotted.
Key evaluation parameter (AUC)
Having obtained the measurement data, pharmacologists analyze graphs depicting the concentration-versus-time relationship. The single most important parameter to extract from these graphs is the area under the curve.
In international practice, this parameter is designated by the abbreviation AUC (from the English term Area Under the Curve). It is precisely the area under the concentration–time curve that allows an objective judgment of the total amount of the drug that entered the circulation over the entire observation period.
Calculation of bioavailability
To translate graphical data into concrete figures, a simple mathematical formula is used. The essence of the interpretation is that the area under the curve for intravenous administration is conventionally taken as the absolute maximum (100%), since there are no losses on the way to the circulation.
Calculation formula: $$F = \frac{AUC_{oral}}{AUC_{IV}} \times 100\%$$
Thus, bioavailability is the ratio of the area under the curve following oral administration of the drug to the area under the curve following its intravenous administration.
Briefly: answers to topical questions
What factors reduce the oral bioavailability of a drug?
The oral bioavailability of a drug is reduced due to barriers in the gastrointestinal tract and liver. The main factors include:
- Physicochemical and enzymatic gastrointestinal factors — destruction of the substance by gastric hydrochloric acid, inactivation by digestive enzymes, and incomplete absorption.
- Intestinal wall metabolism — biotransformation of the substance inside enterocytes (e.g., levodopa (Levodopa)).
- Active transport — efflux of substrates from enterocytes back into the intestinal lumen via P-glycoprotein.
- Presystemic elimination — intensive metabolism during the "first pass" through the liver.
- Increased GI motility — reduction of contact time with the mucous membrane.
Additionally, the bioavailability of certain drugs may be reduced by food intake.
What is presystemic metabolism and how does it affect bioavailability?
Presystemic metabolism (presystemic elimination or first-pass effect) is the loss of a portion of a drug substance before it reaches the systemic circulation upon oral administration. As a result, a smaller amount of the substance enters the systemic circulation than was absorbed from the intestinal lumen. Presystemic elimination can occur due to:
- Metabolism in the liver as the substance passes through the portal circulation.
- Metabolism in the intestinal wall involving the CYP3A4 isoenzyme, as well as the efflux of substances back into the intestinal lumen mediated by P-glycoprotein.
An intensive first-pass effect reduces bioavailability; for some drugs, oral administration may be ineffective, and in certain cases, a dose increase is required.
The formula is easy to remember logically: we divide what we are investigating (oral AUC) by the absolute ideal (IV AUC), and multiply the result by 100%.
Class and exam questions
Why is intravenous administration specifically taken as the reference?
With the intravenous route, the entire administered dose of the drug instantly and without losses enters the systemic circulation, which is why this parameter is taken as 100%.
What does the abbreviation AUC stand for?
AUC stands for Area Under the Curve on a graph of drug concentration versus time.
Why is the same patient used in the experiment?
The test (oral) and reference (IV) administrations are performed on the same patient to eliminate the influence of individual physiological characteristics on the comparison results.
What else to study on this topic
- Total drug clearance
- Volume of distribution of drugs
- Half-life
- Concept of steady-state concentration
- Characteristics of hepatic and portal blood flow
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