The first-pass hepatic metabolism of a number of important therapeutic agents is inconsistent with traditional models that assume that the hepatic extraction ratio of a drug is constant in each individual (independent of the concentration of drug in the hepatic sinusoidal blood and also independent of the history of exposure to the drug). In this review, the authors examine the first-pass metabolism of five "problematic drugs" (propranolol, lidocaine, propafenone, verapamil, and nitroglycerin). Each of these compounds has unique facets to its hepatic clearance and pharmacokinetics as well as striking similarities. Selected aspects of first-pass metabolism are reviewed, and a theory that may explain some of the unusual behavior of the four lipophilic bases (propranolol, lidocaine, propafenone, and verapamil) is presented. Finally, the unusual and variable clearance of nitroglycerin is discussed. D Lalka, RK Griffith, and CL Cronenberger
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First pass metabolism is when some substance (usually a drug) is altered before it can reach its site of action.
Often, drugs that are taken orally are brought by the digestive system into the hepatic portal vein into the liver, which does lots of metabolism. If the same drug could have been administered intravenously (that is, through an injection or line), it would not undergo first pass metabolism because it has bypassed the liver to get into circulation. Eventually, the drug will probably be completely metabolized either way, it's just that the oral route reaches circulation more metabolized than something injected.
the effect after 1st pass effect which is undergone by beta glucoronidase enzyme in small intestine .
If the liver biotransforms the drug extensively into an inactive form, its availability in bioactive form would be greatly reduced before it reaches its site of action
It means the phase of Pharmacokinetic in whic drug has to passed to liver where it is biotranformed or Metabolized and concentration of drug reduced to its orignal concentration.