<P> The first pass effect (also known as first - pass metabolism or presystemic metabolism) is a phenomenon of drug metabolism whereby the concentration of a drug is greatly reduced before it reaches the systemic circulation . It is the fraction of drug lost during the process of absorption which is generally related to the liver and gut wall . Notable drugs that experience a significant first - pass effect are imipramine, morphine, propranolol, buprenorphine, diazepam, midazolam, pethidine, marijuana, cimetidine, lidocaine, and nitroglycerin . </P> <P> First pass metabolism may occur in the liver (for propranolol, lidocaine, chloromethiasole and GTN) or in the gut (for benzylpenicillin and insulin). </P> <P> 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 . </P> <P> 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 . </P>

Which route of administration is most likely to subject a drug to a first pass effect