BIOAVAILABILITY:

Definition: The fractional % of administered drug that reaches the systemic circulation… so if it appears in the systemic circulation its available to the whole body.

If a drug is totally bioavailable, that means that 100% of the drug reaches the systemic circulation.

Typically, bioavailability is less that 100% if the drug is administered orally. So if you take a tablet, there’s some mechanisms by which it is not totally bioavailable.

eg: -If pill doesn’t completely dissolve, but remains as particles in your gut and is excreted, it never reaches the blood so that fraction of it is not bioavailable.

-Pill could absolve but be incompletely absorbed, for one reason or another

-If the pill is ionized in the gut, it won’t be absorbed across the gut wall; drug that remains fully ionized in the gut won’t be absorbed… that effect might be pH dependent (we’ll go over that next week).

Also, a drug may be absorbed, but WHERE is it absorbed to?

First, the drug goes to the portal circulation (blood vessels in close contact with the gut epithelium). That blood goes first to the liver. The liver might kill those drugs, by degradation and metabolism. This is known as first pass metabolism. This happens before the drug gets to the heart, so its not systemic even though it gets into the blood.

eg: -Lidocaine (taken orally) is degraded very effectively by the liver.

The liver can metabolize a drug, but that doesn’t necessarily mean that it inactivates the drug… for example, one or more of the metabolites might be pharmacologically active. Thus, the metabolism by the liver may inactivate the drug, or it may create a metabolite that is active. There are drugs given deliberately in an inactive form, called “pro-drugs”. The liver then acts on them and activates the drugs.

eg: -Cortisone is completely inactive (it’s a pro-drug) but is metabolized to hydro-

cortisone, which is very active.

If a drug is injected INTRA-VENOUSLY (IV), 100% of the drug goes into systemic circulation and is thus 100% bioavailable.

What about a drug that gets into the blood but binds to a protein like albumen?

It IS considered bioavailable because its in the systemic circulation. This is a kind of a subtlety here—it is bioavailable, meaning its potentially available. This is known as the Donan effect, or reservoir effect. It is a drug, not inactivated, bound to a protein. (when we say inactivated in pharmacology, we mean a chemical modification that changes the molecule)

In the systemic circulation there’ll be some fraction of the drug that’s bound to protein. The unbound fraction will be the free molecules that will bind to receptors. As the unbound fraction binds receptors, proteins will release some of the bound molecules to replenish the supply of free molecules. To summarize: the protein bound drug is considered to be bioavailable.

When the drug is bound to albumin (reversibly), it acts as a reservoir to replenish unbound drug when it binds to receptors.

The same concept applies to ionized drug, in the general circulation. Ionized drugs can’t cross cell membranes, but is considered bioavailable because it can revert. If an ionized drug appears in the systemic circulation (not portal) it is considered bioavailable.

Category: Pharmacology Notes