Bioavailability & first-pass
What it means
Bioavailability (F) = fraction of an administered dose reaching the systemic circulation unchanged. IV F = 1.0 by definition. Reduced by incomplete gut absorption, intestinal efflux and first-pass metabolism (gut wall + liver). High first-pass drugs (GTN, propranolol, morphine, lidocaine) need a much larger oral than parenteral dose, or a non-oral route.
Worked example
GTN is given sublingually/transdermally because near-complete hepatic first-pass metabolism destroys an oral dose.
In the exam
A drug is given sublingually rather than swallowed because the liver would otherwise metabolise almost all of an oral dose before it reaches the circulation.
What settles it
First-pass metabolism reduces ORAL bioavailability specifically; it is bypassed by IV/SL/transdermal/PR routes.
Classically confused with
Volume of distribution
Source: StatPearls — Pharmacokinetics