1. Bioavailability

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Medicines contain an active substance, also referred to as Active Pharmaceutical Ingredient (API) and  they are used in order to cure, treat or prevent illness in human beings or in animals. But they can also be used for other purposes, such as diagnosis of certain diseases. In all these use cases, the API must be able to enter the body. But in order to have a therapeutic effect, the API is also needed in the correct dose at the specific site in the body where it has to work. This specific site is referred to as the target site. In addition, the API needs to reach the target within a certain time and to stay there for a defined period.

The rate and degree to which the API is available at the target site is known as bioavailability. This comes closest to defining a “true” or “ideal” bioavailability for a medicine. It is mirrored in the definition by a regulatory authority, the United States FDA. They define bioavailability as "the rate and extent to which the active drug ingredient or therapeutic moiety is absorbed from a drug product and becomes available at the site of drug action", whereas the European EMA simply defines it as “The extent to which an active ingredient is absorbed from a medicine and becomes available in the body”. The latter, while less precise, is however closer to what is measured in reality.

Determining bioavailability

A few points upfront:

  • Bioavailabilty, the fraction of the administered dose which reaches the systemic circulation unchanged, is denoted by the letter f and, if expressed as percent (which is usually the case), by the letter F.

  • Calculation is based on the assumption that there is a direct relationship between the concentration of drug in blood or plasma and the concentration of drug at the site of action. However, consider the possibility that circulating drug levels may misrepresent its availability to its target. (Example: as the only biologically active form of the medicine phenytoin is the free drug, the circulating protein-bound fraction (up to 90%) is not available to its site of action in the brain, even though it might be well-absorbed).

  • When a medicine is given orally, only part of the administered dose appears in the plasma.
    (Example: if 100 mg of a medicine are administered orally and 70 mg of this medicine are absorbed unchanged, the bioavailability is 0.7 or seventy percent).

  • Various factors may affect bioavailability, such as Pharmaceutical factors, Patient related factors, Route of administration, metabolism

The most common type of human bioavailability studies are Plasma Level - Time Studies. Following the administration of a single dose of a medication, blood samples are drawn at specific time intervals and analyzed for drug content