First-pass/Pre-systemic metabolism of Drugs refers to metabolism of a drug during its passage from the site of absorption into the systemic circulation.
The extent of first pass metabolism differs for different drugs and is an important determinant of oral bioavailability.
All orally administered drugs are subjected to First pass metabolism by exposer of drug to drug metabolizing enzymes in the intestinal wall and liver (In liver, Drug first reach through the portal vein).
First-pass/Pre-systemic metabolism can be avoided by administering the drug through sublingual, transdermal or parenteral routes.
Note: Limited First pass metabolism can occur in the skin (transdermally administered drug) and in lungs (for drug reaching venous blood through any route).
When a drug with high first pass metabolism is given orally at higher dose to achieve therapeutic blood levels, the plasma concentration of its metabolites will be much higher compared to those resulting from parenteral dosing of the drug for the same therapeutic level. If the metabolites contribute to the adverse effects of the drug, oral dosing will be less safe than parenteral.
Attributes of drugs with high first pass metabolism
(a) Oral dose is considerably higher than sublingual or parenteral dose.
(b) There is marked individual variation in the oral dose due to differences in the extent of first pass metabolism.
(c) Oral bioavailability is apparently increased in patients with severe liver disease.
(d) Oral bioavailability of a drug is increased if another drug competing with it in first pass metabolism is given concurrently, e.g. chlorpromazine and propranolol.
|High degree of First pass metabolism||Intermediate degree of First pass metabolism||Low degree of First pass metabolism|
Note: Above drug is given orally with high dose
Note: These drugs have high First pass metaboslim in liver so these drug do not given not given orally.
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