First-Pass Metabolism
Definition
Hepatic and gut wall biotransformation of orally absorbed drug before it reaches systemic circulation. Bypassed by IV, intramuscular, inhalation and most dermal routes.
- Site
- Liver and gut wall
- Affected route
- Oral administration
- Bypassed routes
- IV, intramuscular, inhalation, most dermal
- Effect
- Reduces drug reaching systemic circulation
Common questions
Why does first-pass metabolism matter in a poisoning case?+
It explains why an orally ingested toxin can produce a lower blood concentration and different onset timing than the same dose given intravenously, which affects how a toxicologist interprets post-mortem or clinical drug levels against the presumed dose.
Can first-pass metabolism produce a more toxic substance than the one ingested?+
Yes. Hepatic biotransformation sometimes converts a relatively inert parent compound into a more active or toxic metabolite before it ever reaches systemic circulation, so the parent drug's toxicity profile alone can understate the actual clinical risk after oral dosing.
Related terms
- Idiosyncrasy
- A qualitatively abnormal response to a normal dose, traceable to genetic polymorphism in metabolising enzymes, transporters or receptor targets. Not the same...
- LD50
- Median lethal dose; the dose of a substance that kills 50% of a test population, expressed as mg/kg body weight. The classical...
- Pharmacogenomics
- Study of how inherited variation in drug-metabolising genes (CYP2D6, CYP2C19, NAT2, G6PD) changes drug response. The Indian Genome Variation Consortium and ICMR...
- Tolerance
- Reduced response to a given dose after repeated exposure. Pharmacokinetic tolerance is enzyme induction or transporter upregulation; pharmacodynamic tolerance is receptor downregulation...
- Volume of Distribution (Vd)
- The apparent volume in which a drug is distributed in the body, calculated as dose divided by plasma concentration at time zero....