Bioavailability is another primary pharmacokinetic parameter (like Clearance and Volume of Distribution) that describes the fraction of administered drug that reaches the systemic circulation. As a fraction, bioavailability can take any real value between 0 and 1 (e.g. 0.54). Sometimes this is reported as a percentage instead of a decimal (e.g. 54%).
To explain this, think about your most recent paycheck (Example Pay Stub from www.youngmoney.com). You generally have a few basic categories on that paycheck such as Gross Pay (blue box on Example Pay Stub), Taxes, and Net Pay (red box on Example Pay Stub). For this example, let’s say your Gross Pay was $1000; and let’s assume that your Taxes (all totaled together) were $250. You could calculate the Net Pay (i.e. the money you get to put in your bank account!) by subtracting the Taxes from the Gross Pay.
The equations that relate Gross Pay, Taxes, and Net Pay look like this:
In this example, the amount of money the company paid out was $1000 (Gross Pay), but the amount of money you actually received to put in your bank was only $750 (Net Pay). The remaining $250 was “lost” to Taxes. The Gross Pay represents the amount of drug administered. The Net Pay represents the amount of drug that is usable by the body (i.e. reaches systemic circulation). And the Taxes represent the amount of drug that is “lost” between drug administration and the systemic circulation.
Another way to look at this is to assume that Taxes will always be proportional to the Gross Pay. The example above would then look like this:
Thus, the Net Pay is 75% of the Gross Pay; or the amount of drug in the systemic circulation is 75% of the administered dose. This is the bioavailability of the drug. The fractional of administered drug that reaches the systemic circulation. The reason we use fractional amounts is that it is very easy to calculate the amount of drug administered. However, it is very difficult to calculate the amount of drug in the systemic circulation. Thus we calculate the percentage of drug that reaches the systemic circulation relative to something that we assume to be 100% bioavailable (i.e. direct intravenous injection).
Now that we have established a definition for bioavailability, here are a few common uses for the term bioavailability:
- Absolute bioavailability: The bioavailability of a non-intravenous route of administration relative to the same drug administered intravenously. Intravenous administration is assumed to be 1 or 100%.
- Example: The oral formulation has an absolute bioavailability of 62%.
- Relative bioavailability: The bioavailability of a non-intravenous route of administration relative to another non-intravenous route of administration. The reference route of administration is assumed to be 100%.
- Example: The capsule has a relative bioavailability of 62% when compared to the tablet.
- Example: The pressed tablet has a relative bioavailability of 130% when compared to the gelcap.
- Note that relative bioavailability does not have an upper constraint of 1 (or 100%).
- Oral bioavailability: The absolute bioavailability of an oral dosage form (e.g. capsule, tablet, solution, etc.).
The key to staying on track with the bioavailability parameter is to understand what the reference point is during the discussion. One simple way to address that is to ask, “Do you mean absolute bioavailability or relative bioavailability?” Or perhaps you could ask, “The bioavailability you are quoting is relative to what route of administration?” If you can get those two questions answered, you will be clear on which “bioavailability” is under discussion. Good luck!
Today’s pharmacokineticists and PK/PD modelers are under more pressure than ever to quickly and accurately characterize the safety and efficacy profiles of investigational drugs. They need the right tools to perform non-compartmental analysis (NCA), build pharmacometric models, and generate reports that communicate their findings.
Phoenix 7.0’s new features and enhancements are the direct result of user feedback we received to make the world’s most advanced PK/PD software package even better.
Watch this webinar to learn how Phoenix 7.0 helps you handle bigger datasets, perform lightning-fast NCA, and make gorgeous plots.