Bioavailability

The term bioavailability is used very frequently in pharmacokinetic discussions. Often it is misused and complicated by those who don’t understand its meaning. Bioavailability simply means the fraction of administered drug that reached the systemic circulation (blood). It can range from 0% (no drug) to 100% (all of the administered drug).

Absolute vs Relative

The adjectives “absolute” and “relative” are commonly added to the bioavailability term. “Absolute” bioavailability is the amount of drug from a formulation that reaches the systemic circulation relative to an intravenous (IV) dose. The IV dose is assumed to be 100% bioavailable … since you are injecting the drug directly into the systemic circulation. “Relative” bioavailability is the amount of drug from a formulation that reaches the systemic circulation relative to a different formulation (non-IV) such as oral solution, reference formulation, etc. Relative bioavailability is commonly used when an IV formulation does not exist or cannot be made.

First-pass effect

When working with oral formulations, you may hear something about the “first-pass” effect. This refers to the drug lost between oral administration and first appearance in the systemic circulation. The drug must survive the milieu in the gastrointestinal (GI) tract, cross the gut wall, and then pass through the portal vein to the liver. If a drug molecule survives that gauntlet, it will reach the systemic circulation.

Let’s take an example with 100 drug molecules that are ingested in pill form. Only 90 of those molecules survive the GI tract. Then 81 make it past the gut wall and into the portal vein. Of the 81 that enter the liver, only 41 make it to the systemic circulation. Thus the bioavailability is 41/100 = 41%. We also know the fraction that passed the gut (90/100 = 90%), the gut wall (81/90 = 90%), and the liver (41/81 = 50%). If you multiply each of those fractions together (90% * 90% * 50% = 41%) you arrive at the total bioavailability for the drug.

This information is very helpful because we can see that the liver metabolism is the biggest challenge with increasing bioavailability. Increases in solubility and gut wall permeability will not significantly improve the bioavailability. If, however, we could modify the drug molecule to avoid some liver metabolism, we might be able to increase bioavailability significantly.

Calculating bioavailability

Bioavailability is calculated as the ratio of area under the curve (AUC) for the test and reference formulation/route of administration. If you are calculating the absolute bioavailability, it would be calculated as:

 F = \frac{AUC_{oral}}{AUC_{IV}}

If you were calculating the relative bioavailability, it would be:

 F_{rel} = \frac{AUC_{formulation_/}}{AUC_{formulation_2}}

So keep bioavailability simple in your mind, and you will be successful in your future PK discussions.

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