Bioavailability and Bioequivalence
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.
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
- When a
medicine is given orally, only part of the administered dose appears in
(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