First-pass metabolism and prodrugs
Explains why some drugs don't work orally — and why others only work after being metabolized.
Where this fitsConnects to 2 · Unlocks 1
- Connects to
- Absorption and routes of administration — Oral drugs pass through gut and liver before the brain.
- When enzymes change: induction, inhibition and genetics — Inhibiting the first-pass enzyme changes everything.
- Unlocks
- Half-life and redistribution — With delivery understood, turn to how long drugs last.
Walk through
The first pass
Swallowed drug is absorbed from the gut into blood that goes to the liver first. Enzymes there (and in the gut) break some down before it reaches the brain.
Analogy and worked example
Analogy: A customs checkpoint on the only road from the port (gut) to the capital (brain): a lot of cargo gets confiscated (first pass). Fly in directly (inhale, inject) and you skip customs. Or bribe the officers (MAO inhibitor) and everything gets through. A prodrug is a flat-pack kit that only works once customs assembles it.
Why is lisdexamfetamine considered to have lower abuse potential than amphetamine?
- It's a prodrug: inactive until converted to amphetamine.
Tip: the ← and → keys move through the lesson.
Full lesson: Prodrugs and first-pass metabolism