the route of administration that is most likely to subject a drug to a first pass effect is by mouth.
which route of administration is most likely to subject a drug to a first pass effect?
by mouth
after a drug is swallowed, it is absorbed by the digestive system and enters the hepatic portal system. it is carried through the portal vein into the liver before it reaches the rest of the body. the liver metabolizes many drugs, sometimes to such an extent that only a small amount of active drug emerges from the liver to the rest of the circulatory system. this "first pass" through the liver thus greatly reduces the bioavailability of the drug.
first pass effect
the four primary systems that affect the first pass effect of a drug are the enzymes of the gastrointestinal lumen, gut wall enzymes, bacterial enzymes, and hepatic enzymes.





























in drug design, drug candidates may have good druglikeness but fail on first-pass metabolism because it is biochemically selective.





























alternative routes of administration like suppository, intravenous, intramuscular, inhalational aerosol, transdermal and sublingual avoid the first-pass effect because they allow drugs to be absorbed directly into the systemic circulation.
first pass effect