Putting a number on "how much arrives"
Bioavailability, written F, is the fraction of an administered dose that reaches the systemic circulation in active form. By definition an IV dose has F = 1 (100%). For any other route we compare how much total drug exposure it produces against the IV exposure. "Total exposure" is measured by the area under the curve — the area under a plot of blood concentration over time.
Absolute bioavailability:
AUC(oral) Dose(IV)
F = --------- x ----------
AUC(IV) Dose(oral)
Worked example:
100 mg oral -> AUC = 40 mg.h/L
100 mg IV -> AUC = 80 mg.h/L
F = (40 / 80) x (100 / 100) = 0.50 -> 50%
So only HALF of the swallowed 100 mg reaches the blood intact.
To match an IV effect you would need roughly a 200 mg oral dose.Two things can lower F: the drug may simply fail to be absorbed (poor dissolution, destruction by stomach acid, or being pumped back out by the gut wall), or it may be absorbed fine but then destroyed before it reaches the general circulation. That second loss is the first-pass effect.
The liver takes its cut
After absorption from the gut, blood travels through the portal vein straight to the liver before joining the rest of the body. The liver is the body's chemical factory, and it can metabolise a swallowed drug heavily on this very first pass — hence the first-pass effect, also called first-pass metabolism or presystemic elimination. For some drugs the liver removes 70–90% before a single molecule reaches the heart.
How much the liver removes is captured by the hepatic extraction ratio. A high-extraction drug loses most of an oral dose to first pass, so its oral F is low and we often have to give a much bigger oral dose — or switch to a route that skips the liver. This is exactly why nitroglycerin is given sublingually and not swallowed: orally, the liver would obliterate it.