First pass metabolism
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First pass metabolism
It is also increased if another drug competing with it in first pass metabolism is given concurrently. Discrimination between the 2 models may be performed under linear conditions in which all pharmacokinetic parameters are independent of concentration and time. Therefore the oral bioavailability of the drug is reduced. Models that describe the dependence of bioavailability on changes in these physiological variables have been developed for drugs subject to first-pass metabolism only in the liver. Notable drugs that experience a significant first-pass effect are imipramine , morphine , propranolol , buprenorphine , diazepam , midazolam , pethidine , cannabis , cimetidine , lidocaine , and nitroglycerin. Cytochrome P enzymes are found in high concentrations in the liver. Phase II: Combination of a glucuronic acid, sulfuric acid, acetic acid or amino acid with a functional group to form a polar conjugate that can be readily excreted in urine or feces. This version of the course is no longer available. First-pass elimination takes place when a drug is metabolised between its site of administration and the site of sampling for measurement of drug concentration. Metabolic products are often less active pharmacodynamically than the parent drug and may even be inactive. Related terms Prodrug Enzyme induction: Acceleration of metabolism by increase of enzyme expression. One major therapeutic implication of extensive first-pass metabolism is that much larger oral doses than intravenous doses are required to achieve equivalent plasma concentrations. Enzyme inhibition: Competitive blockade or inactivation of the enzyme by a substance, which may or may not be a substrate. The liver is usually assumed to be the major site of first-pass metabolism of a drug administered orally, but other potential sites are the gastrointestinal tract, blood, vascular endothelium, lungs, and the arm from which venous samples are taken. Drugs with high first pass effect have a considerably higher oral dose than sublingual or parenteral dose.
Cytochrome P enzymes are found in high concentrations in the liver. Metabolic products are often less active pharmacodynamically than the parent drug and may even be inactive.
Examples of drugs exhibiting first pass metabolism are aspirin and lidocaine. Enzyme inhibition: Competitive blockade or inactivation of the enzyme by a substance, which may or may not be a substrate.
Two that have been applied widely are the 'well-stirred' and 'parallel tube' models. Two phases in metabolism are classically recognized: Phase I: Transformation of drug into a more polar metabolite by introducing or unmasking a functional group e.
For prodrugs, inhibition may decrease the pharmacological response.
based on 14 review