Metabolism of Sedatives in Liver Disease

  • Steven Schenker
  • Anastacio M. Hoyumpa
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 272)


The liver has a key role in drug disposition and elimination. This is by virtue of 1) its strategic location astride the portal vein and 2) its large enzymatic complement for drug metabolism. The first of these, location along intestinal venous drainage, implies that drugs absorbed via the gastrointestinal tract will initially enter the liver and be excluded from the systemic circulation (presystemic or first pass effect). To the extent that such absorbed drugs are metabolized within the liver or are shunted around it, concentrations of the parent drug in blood and target organs will vary. Drugs with extensive hepatic metabolism are thus likely to be affected the most with liver disease- and/or shunting. The bioavailability of such agents (see later) in such a setting is likely to be increased, leading to a lesser first pass effect and toxic side effects may ensue. As regards the second point, the liver has the largest amount of biotransforming enzymes for most drugs. It contributes also importantly to the removal of some drugs via biliary excretion. Thus, impairment of either process, as with liver disease, is likely to decrease drug removal and may result in drug accumulation and ultimately in its toxicity. It is evident, therefore, that liver disease and drug metabolism are closely related processes (1).


Liver Disease Chronic Liver Disease Hepatic Encephalopathy Drug Disposition Intrinsic Clearance 
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Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Steven Schenker
    • 1
  • Anastacio M. Hoyumpa
    • 1
  1. 1.Department of Medicine Division of Gastroenterology and NutritionThe University of Texas Health Science CenterSan AntonioUSA

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