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Effect of Hepatic Disease on Pharmacokinetics: Active Drug, Metabolite and Fraction of Metabolized Drug01:14

Effect of Hepatic Disease on Pharmacokinetics: Active Drug, Metabolite and Fraction of Metabolized Drug

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In pharmacotherapy, monitoring drug concentrations is paramount, especially for drugs whose therapeutic effects hinge on both the active compound and its metabolite. Hepatic impairment profoundly influences drug potency by altering liver function. If the drug is more potent than its metabolite, impaired liver function amplifies drug activity due to elevated drug concentration levels. Conversely, if the metabolite holds greater potency, diminished liver function diminishes drug activity by...
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Chronic liver disease significantly impacts drug metabolism due to alterations in hepatic blood flow and enzyme accessibility. This disruption affects the body's pharmacokinetics—the movement and processing of drugs within the system. Key enzymes crucial for metabolizing medications become less accessible, changing how drugs are processed and utilized. Furthermore, liver disease influences the synthesis of plasma proteins, such as albumin and globulins, which play critical roles in drug...
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The liver plays a pivotal role in eliminating drugs and their metabolites, primarily through a process known as biliary excretion. This process involves the hepatocytes, the primary cells in the liver that generate bile. A range of transporters actively expels polar drugs or hydrophilic drug metabolites into the bile, which transports the drugs and metabolites into the small intestine. From here, they are eventually expelled from the body through feces. In some instances, the original drug or a...
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Drug Biotransformation: Overview01:16

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Pharmaceutical substances known as xenobiotics are predominantly lipophilic and nonionized. This enables them to permeate lipid bilayers, such as cell membranes, and interact with intracellular target receptors. Lipophilic drugs have an advantage in crossing biological barriers and reaching their intended sites of action. However, lipophilic drugs often have a restricted capacity for renal expulsion or elimination from the body. When these drugs enter the kidneys and undergo glomerular...
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Biotransformation, also known as drug metabolism, is a vital physiological process that chemically alters drugs, facilitating their elimination from the body and terminating their action. This process involves two main phases: phase I and phase II reactions. Phase I reactions, including oxidation, reduction, and hydrolysis, introduce or unmask polar functional groups on the drug molecule, thereby increasing its water solubility. By enhancing water solubility, the drug becomes more hydrophilic...
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Phase II reactions are essential for the detoxification and elimination of drugs from the body. These reactions involve the conjugation of parent drugs or their phase I metabolites with endogenous molecules, resulting in more hydrophilic drug conjugates. The primary conjugation reactions in this phase are sulfation and glucuronidation. Both sulfation and glucuronidation typically produce biologically inactive metabolites. However, in some cases involving prodrugs, active metabolites may be...
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Related Experiment Video

Updated: Jan 11, 2026

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
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Extrahepatic drug metabolizing enzymes.

J Kapitulnik1, H W Strobel

  • 1Department of Pharmacology, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Israel.

Journal of Biochemical and Molecular Toxicology
|July 14, 1999
PubMed
Summary

Extrahepatic drug-metabolizing enzymes show unique regulation tied to tissue function. Hormonal effects on these enzymes may involve tissue-specific transcription factor activity.

Area of Science:

  • Pharmacology
  • Biochemistry
  • Molecular Biology

Background:

  • Drug metabolizing enzymes (DMEs) are crucial for xenobiotic and endogenous compound metabolism.
  • While hepatic DMEs are well-studied, extrahepatic DME activity is increasingly recognized.

Purpose of the Study:

  • To review the unique regulatory mechanisms of extrahepatic DMEs.
  • To explore the association between DME regulation, tissue function, and hormonal influences.

Main Methods:

  • Literature review of studies investigating extrahepatic DME expression and activity.
  • Analysis of evidence for tissue-specific regulation and hormonal control.

Main Results:

  • Expression and activity of several extrahepatic DMEs are uniquely regulated, correlating with specific tissue functions.

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  • Hormonal regulation of these enzymes may occur via tissue-specific transcription factor distribution and responses.

    • Conclusions:

    • Extrahepatic DME regulation is complex and tissue-specific, differing from hepatic patterns.
    • Hormonal influences play a significant role, mediated by tissue-specific molecular mechanisms.