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Hepatic Drug Excretion: Influencing Factors01:16

Hepatic Drug Excretion: Influencing Factors

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The biliary system of the liver, crucial for bile secretion and drug excretion, comprises intrahepatic bile ducts that merge to form the common hepatic duct. This duct, carrying hepatic bile, combines with the cystic duct, draining the gallbladder and forming the common bile duct, which empties into the duodenum. Bile, produced by hepatic cells lining the bile canaliculi, is composed primarily of water, bile salts, pigments, electrolytes, and lesser amounts of cholesterol and fatty acids. Bile...
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Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow01:26

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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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Hepatic Drug Excretion: Enterohepatic Cycling01:17

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Enterohepatic cycling involves the active secretion of drugs and their metabolites into the bile via transporters in the canalicular membrane of hepatocytes. This secretion is an integral part of the digestive process, releasing these substances into the gastrointestinal (GI) tract.
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Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test01:22

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In clinical practice, the direct measurement of hepatic blood flow to evaluate liver function presents significant challenges due to the intricate and specialized nature of the necessary techniques. Consequently, healthcare professionals often rely on empirical estimates derived from thorough patient examinations and liver function tests to gauge liver health. Among the tools at their disposal, the Child–Pugh and MELD scoring systems stand out for their ability to categorize and assess...
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Pharmacokinetics in Obese Patients: Drug Metabolism and Excretion01:20

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Drug metabolism, a critical process in the liver, involves two primary phases: Phase I reactions and Phase II conjugation. Obesity introduces significant alterations in this metabolic process, primarily due to fatty infiltration of the liver, leading to conditions such as nonalcoholic fatty liver disease (NAFLD). This condition can modify the activities of both Phase I and II enzymes, impacting how drugs are metabolized in obese patients.Phase I metabolism sees variable effects across...
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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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Hepatitis C eradication with sofosbuvir leads to significant metabolic changes.

Amilcar L Morales1, Zachary Junga1, Manish B Singla1

  • 1Amilcar L Morales, Hepatology Service, San Antonio Military Medical Center, San Antonio, TX 78234, United States.

World Journal of Hepatology
|January 5, 2017
PubMed
Summary

Hepatitis C treatment with sofosbuvir (SOF) regimens significantly lowered hemoglobin A1C (HbA1C) in patients with diabetes. However, these effective HCV therapies also led to increased LDL and total cholesterol levels post-treatment.

Keywords:
Hemoglobin A1cHepatitis CHyperlipidemiaLow-density lipoproteinSofosbuvir

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Area of Science:

  • Hepatology
  • Endocrinology
  • Cardiovascular Science

Background:

  • Hepatitis C virus (HCV) infection poses significant health challenges.
  • Understanding the systemic effects of antiviral therapies is crucial for comprehensive patient care.
  • Sofosbuvir (SOF)-based regimens have revolutionized HCV treatment, but their impact on metabolic parameters requires further investigation.

Purpose of the Study:

  • To evaluate the influence of sofosbuvir (SOF)-based regimens on glycemic control, specifically hemoglobin A1C (HbA1C).
  • To assess the impact of SOF-based therapies on lipid profiles, including low-density lipoprotein (LDL) and total cholesterol (TC).
  • To analyze metabolic changes in HCV-infected patients following successful SOF treatment.

Main Methods:

  • Retrospective analysis of 60 HCV-infected patients treated with SOF regimens (SOF/ribavirin/interferon, SOF/simeprevir, or SOF/ledipasvir ± ribavirin).
  • Inclusion criteria required HbA1C and lipid panel data within six months pre- and post-therapy.
  • Exclusion of patients with new medications or adjustments for hyperlipidemia or diabetes mellitus (DM).

Main Results:

  • A significant decrease in HbA1C was observed post-HCV treatment (6.66% ± 0.95% to 6.14% ± 0.65%, P < 0.005), particularly in patients with type 2 DM.
  • Patients treated with SOF/ledipasvir showed a trend towards a lower HbA1C response compared to other regimens (P = 0.070).
  • Significant increases in LDL (99.5 ± 28.9 to 128.3 ± 34.9 mg/dL, P < 0.001) and TC (171.6 ± 32.5 to 199.7 ± 40.0 mg/dL, P < 0.001) were noted post-treatment.

Conclusions:

  • Eradication of HCV using SOF-based regimens leads to a significant improvement in glycemic control, evidenced by reduced HbA1C levels.
  • Successful HCV treatment with SOF regimens is associated with adverse changes in lipid profiles, including elevated LDL and TC.
  • These findings highlight the importance of monitoring metabolic parameters in patients undergoing antiviral therapy for HCV.