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Related Experiment Videos

Decrease in albendazole sulphonation during experimental fascioliasis in sheep.

P Galtier1, M Alvinerie, Y Plusquellec

  • 1Laboratoire de Pharmacologie-Toxicologie INRA, Toulouse, France.

Xenobiotica; the Fate of Foreign Compounds in Biological Systems
|July 1, 1991
PubMed
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Fasciola hepatica infection in sheep impairs albendazole metabolism, significantly reducing albendazole sulphonation and increasing drug persistence. This impacts anthelmintic efficacy in parasitic infections.

Area of Science:

  • Veterinary Pharmacology
  • Parasitology
  • Drug Metabolism

Background:

  • Albendazole is a broad-spectrum anthelmintic widely used in livestock.
  • Fasciola hepatica infection can alter host physiology and drug pharmacokinetics.
  • Understanding drug metabolism changes during parasitic infections is crucial for effective treatment.

Purpose of the Study:

  • To investigate the in vivo S-oxidation of albendazole in sheep infected with Fasciola hepatica.
  • To determine the pharmacokinetic profile of albendazole sulphoxide and sulphone post-infection.
  • To correlate changes in drug metabolism with parasitic pathology.

Main Methods:

  • Pharmacokinetic analysis of albendazole, albendazole sulphoxide, and sulphone in sheep.
  • Measurement of plasma antibodies against Fasciola hepatica.

Related Experiment Videos

  • Assessment of liver microsomal enzyme activity, including cytochrome P450-dependent monooxygenases.
  • In vitro sulphonation assays using liver microsomes.

    • Main Results:

    • Fasciola hepatica infection significantly decreased the conversion of albendazole to its active metabolite, albendazole sulphoxide, by 58% at 8 weeks post-infection.
    • The elimination rate of albendazole sulphone was reduced by 87% at 8 weeks post-infection.
    • Increased plasma concentrations and prolonged residence time of albendazole sulphone were observed between 4-12 weeks post-infection.
    • Impaired sulphonation was linked to decreased liver microsomal cytochrome P450 activity.

    Conclusions:

    • Fasciola hepatica infection transiently impairs albendazole sulphonation in sheep.
    • The observed metabolic changes can lead to altered drug efficacy and increased drug exposure.
    • Cytochrome P450 inhibition by parasitic infection is a potential mechanism for reduced albendazole metabolism.