{"id":86,"date":"2019-04-24T12:15:33","date_gmt":"2019-04-24T12:15:33","guid":{"rendered":"https:\/\/sepia2.unil.ch\/pharmacology\/?page_id=86"},"modified":"2019-04-26T13:57:45","modified_gmt":"2019-04-26T13:57:45","slug":"metabolism","status":"publish","type":"page","link":"https:\/\/sepia2.unil.ch\/pharmacology\/mechanisms\/metabolism\/","title":{"rendered":"Metabolism"},"content":{"rendered":"\n

“Drug biotransformation, generally into more polar compounds readily excreted from the body through urine or feces” <\/h2>\n\n\n\n

Description<\/h3>\n\n\n\n
\n
\n

By definition, a drug administered intravenously<\/a> undergoes immediate and complete absorption. By contrast, drugs administered extravascularly<\/a> need to be carried through various barriers in order to be able to reach the blood circulation and then their site of action. <\/p>\n\n\n\n

Metabolic biotransformations can occur between \nabsorption of the drug into the general circulation and its excretion. \nMetabolic products are often less active pharmacodynamically than the \nparent drug and may even be inactive. However, some metabolites have \nenhanced activity or toxic properties.\n<\/p>\n<\/div>\n\n\n\n

\n
  1. Phase\n I: Transformation of drug into a more polar metabolite by introducing \nor unmasking a functional group (e.g. oxidation, reduction or \nhydrolysis). Oxidation reactions are often catalyzed by a member of the \ncytochrome P450 family. These enzymes are mostly located in the \nendoplasmic reticulum of the hepatocytes (microsomial enzymes).<\/li>
  2. Phase\n II: Combination of a glucuronic acid, sulfuric acid, acetic acid or \namino acid with a functional group to form a polar conjugate that can be\n readily excreted in urine or feces. The enzymes catalyzing these \nreactions are mostly located in the cytosol of the hepatocytes.<\/li><\/ol>\n\n\n\n

    These two phases often occur sequentially: phase I oxidation prepares a functional radical enabling the conjugation with a polar compound.<\/p>\n\n\n\n

    Clinical implications<\/h3>\n\n\n\n

    Metabolic reactions widely vary from one \nindividual to another, and consequently affect the dose and frequency of\n administration required to achieve effective and safe drug levels in \nthe organism. Genetic polymorphism accounts for some of the differences \nobserved. Other important factors determining metabolism are age, diet, \nenvironmental factors, drug-drug interactions and diseases affecting \nmetabolism (e.g. acute or chronic liver, cardiac or renal disorders).<\/p>\n\n\n\n

    Related terms<\/h3>\n\n\n\n

    Prodrug<\/a>\n<\/p>\n\n\n\n

    Enzyme induction: Acceleration of metabolism by \nincrease of enzyme expression. Various substrates appear to induce \nmetabolism, such as certain drugs and environmental pollutants. \nInduction decreases the pharmacological action of the substrate of the \nenzyme, including frequently the inducer. Sometimes, the enhanced amount\n of metabolites can increase toxicity or carcinogenicity.\n<\/p>\n\n\n\n

    Enzyme inhibition: Competitive blockade or \ninactivation of the enzyme by a substance, which may or may not be a \nsubstrate. The inhibition increases concentrations of the parent drug, \nand thus exaggerates and prolongs its pharmacological effects. For \nprodrugs, inhibition may decrease the pharmacological response.\n<\/p>\n\n\n\n

    Hepatic first pass effect: All drug dose absorbed \nfrom the gastrointestinal tract is first delivered to the liver by the \nportal vein. A fraction of the drug can then be metabolized in the liver\n before it even reaches the systemic circulation. Therefore the oral bioavailability<\/a> of the drug is reduced.<\/p>\n","protected":false},"excerpt":{"rendered":"

    “Drug biotransformation, generally into more polar compounds readily excreted from the body through urine or feces” Description By definition, a drug administered intravenously undergoes immediate and complete absorption. By contrast, drugs administered extravascularly need to be carried through various barriers in order to be able to reach the blood circulation and then their site of … <\/p>\n

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