Simvastatin first pass metabolism

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  • In fact, this is the only FDA-approved route of drug
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  • However, metabolism of statins could be susceptible to OATP
  • The major metabolite, β-hydroxyacid-simvastatin, is the most potent with respect to HMG-CoA reductase inhibition

    Metabolism Elimination; Simvastatin: T max 4 hours Bioavailability <5%: 95% bound to plasma Once absorbed into the portal venous system, while all statins undergo extensive first-pass metabolism, the rate of this first-pass hepatic uptake inversely relates to the systemic

    Simvastatin is a medication with a significant problem of substantial first-pass metabolism, which results in a very low bioavailability of only 5%

    2005 Feb;19 (1):117-25

    Metabolism

    Because of the extensive CYP3A4-mediated metabolism already during the first pass, simvastatin has a low mean oral bioavailability of about 5%[2, 3]

    The AUCs of such CYP3A4 substrates are remarkably changed by the inhibition, induction, and saturation of CYP3A4 and so prediction of intestinal first-pass metabolism is important

    2

    Pharmacokinetic measures involve the rate of absorption, distribution, metabolism, and excretion for these molecules

    Which medication that Mrs

    - have substantial first pass metabolism in the duodenum and the jejunum (proximal parts of SI) as the drug would already be released from the gut in these areas Given that the liver is the target organ for statins, efficient first-pass uptake may be more important than high bioavailability for statin effect

    In plasma, nearly 95% of statins and their metabolites are protein-bound [14,16]

    Simvastatin (sim" va stat' in) is an orally available inhibitor of hepatic 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the major rate-limiting enzyme in cholesterol synthesis

    Troglitazone has been reported to reduce the effect of simvastatin, probably by induction of CYP3A4 [94]

    In the other primary route the inactive lactone prodrug is hydrolysed to the pharmacologically active simvastatin acid by carboxyl esterases and also non-enzymatically

    Oral absorption is rapid and the bioavailability low due to an extensive first-pass metabolism

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