For example, a drug that is taken orally must go through the digestive system before reaching the circulatory system. Some of the drug is destroyed in the digestive tract, and the rest is metabolised by liver enzymes. Hence, only some part of the drug given may actually be bioavailable.
What does bioavailability mean?
Bioavailability indicates the amount of the dose taken that makes it to the bloodstream without any alterations.
It is believed that an IV dose has a bioavailability of 100% because the drug gets into the bloodstream. Other forms of drug delivery may have lower bioavailability rates.
For instance, when a patient takes a medicine orally, it must withstand digestion, cross the intestinal wall and may undergo first-pass metabolism in the liver. All these mechanisms can decrease the amount of the drug that enters the systemic circulation.
Bioavailability is usually expressed as a percentage. In practice, it is usually calculated by means of AUC (area under the curve) measurements.
Why does bioavailability matter?
The bioavailability of a substance will influence the dose and frequency of drug administration.
A drug having low bioavailability may have to be administered in larger doses than a drug that is effective despite having high bioavailability. Even with low bioavailability, the drug may still work. It may simply be poorly absorbed, unstable or extensively metabolised.
The route of administration can also make a significant difference. A compound may behave differently when delivered orally, subcutaneously, intramuscularly or intravenously.
This is particularly relevant in peptide research. Numerous peptides are prone to enzymatic degradation and may not be absorbed well through oral routes. Hence, researchers explore various delivery methods and formulations to assess the efficiency of peptides in terms of their access to systemic circulation.
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What affects bioavailability?
There are various factors that may affect bioavailability.
The route of administration is one of the most important aspects to consider. With intravenous administration, a drug does not undergo any of the steps associated with absorption, while oral administration involves digestion, absorption, and first-pass metabolism.
Furthermore, it is important to consider the stability of the substance. Some substances might not reach the bloodstream in an unchanged state. Some peptides are known to undergo enzymatic hydrolysis prior to getting into systemic circulation.
The process of absorption acts to a certain extent based on different parameters such as size, charge, and solubility, while these properties can also influence the ease of moving across biological membranes.
Food consumption alters the process of absorption in a variety of ways, for instance, by speeding up gastric emptying or intestinal conditions and by modifying the interactions of a compound with substances in the gut.
Metabolism acts as a reducing agent for the systemic exposure of the substance. For instance, metabolism in the gut and liver may alter a substance before its entry into blood circulation.
Finally, formulation is an important aspect of bioavailability. Alterations affecting the chemical form of the substance, the delivery mechanism or even certain components of the formulation can influence the absorption time and quantity of the substance in the blood.
Absolute and relative bioavailability
Two terms commonly used are absolute bioavailability and relative bioavailability.
Absolute bioavailability compares exposure from a non-intravenous route with exposure following intravenous administration. Since an IV dose enters the bloodstream directly, it provides the reference for complete systemic availability.
Relative bioavailability compares two different formulations or administration routes. Researchers may, for example, compare two formulations of the same compound to determine whether one produces greater systemic exposure.
Bioavailability and pharmacokinetics
Bioavailability is closely related to pharmacokinetics, but the terms are not interchangeable.
Pharmacokinetics studies the processes that a drug undergoes in the body over time, including its absorption, distribution, metabolism, and excretion.
Bioavailability is concerned with the proportion of the administered drug that reaches the systemic circulation.
Bioavailability can be measured by determining pharmacokinetic parameters such as AUC, Cmax and Tmax. In fact, these parameters describe aspects of systemic exposure in relation to absorption and the timing of absorption.
Bioavailability in peptide research
Bioavailability is particularly important for peptides because they can present specific delivery challenges.
Many peptides are relatively large and may be unstable in the gastrointestinal environment. Proteolytic enzymes could have the ability to divide peptide chains into smaller fragments and lessen the amount of the full peptide that is absorbed.
For this reason, scientists search for other ways of administering the peptide.
Nonetheless, increased bioavailability does not always indicate a specific biological or pharmacological effect. Systemic exposure is only one part of the wider research picture. Pharmacodynamics, target engagement, metabolism and safety also need to be considered.
How is bioavailability measured?
Generally, bioavailability is studied through pharmacokinetic studies. Scientists take measurements on the sample concentration of a particular compound found in biological specimens, especially in plasma or blood, over a specific period following the administration.
The resulting concentration-time data can be analysed to determine measures such as AUC and Cmax.
Study design is important because factors including dose, formulation, administration route, sampling schedule and study population can influence the results.
A reported bioavailability value should therefore be interpreted in the context of how it was measured.
Bioavailability vs absorption
Absorption and bioavailability are related but not identical.
Absorption refers to the movement of a substance from its administration site into systemic circulation. Bioavailability deals with the amount of a substance administered to a patient that becomes accessible in systemic circulation.
If a compound is absorbed through the intestines, its bioavailability is still considered low if a large part of the compound is metabolised before it reaches systemic circulation.
Why the term matter in research?
Bioavailability is a concept that allows researchers to determine how the method of administration relates to systemic exposure and is applicable to drug formulation and development, pharmacokinetics, determining the dose and comparing different routes of administration.
However, bioavailability is not merely an indication of effectiveness. Rather, it informs researchers of the degree of availability for systemic circulation of any administered material or compound.
Stress that bioavailability is particularly meaningful for the exploration of the bioactivity of peptides and other biologically active substances.
Research Use Only. This glossary explains terminology used in published research. It is not medical advice and does not describe any product for human or animal use.