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Related Experiment Videos

Lorazepam: glucuronide formation in the cat.

R T Schillings, S F Sisenwine, M H Schwartz

    Drug Metabolism and Disposition: the Biological Fate of Chemicals
    |March 1, 1975
    PubMed
    Summary

    Domestic cats excrete lorazepam (a sedative) and its primary metabolite, lorazepam glucuronide, mainly through urine and feces. This study demonstrates cats effectively use glucuronidation for drug metabolism, challenging previous assumptions.

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    Area of Science:

    • Pharmacology
    • Veterinary Medicine
    • Drug Metabolism

    Background:

    • Cats are often reported to have limited capacity for glucuronidation, a key metabolic pathway for many drugs.
    • Understanding lorazepam metabolism in cats is crucial for appropriate therapeutic use and drug development.

    Purpose of the Study:

    • To investigate the excretion and metabolism of lorazepam in domestic cats.
    • To determine the primary routes of lorazepam elimination and identify major metabolites.
    • To assess the role of glucuronidation in feline drug metabolism.

    Main Methods:

    • Oral administration of radiolabeled 14-C-lorazepam to domestic cats.
    • Quantification of radioactivity in urine and feces over time.
    • Identification and structural confirmation of urinary metabolites using chemical analysis and mass spectrometry.

    Main Results:

    • Approximately 47.3% of the lorazepam dose was excreted in urine and 54.0% in feces.
    • Lorazepam glucuronide was identified as the major urinary metabolite, accounting for 29% of the dose within 3 days.
    • Chemical analysis and mass spectrometry confirmed the structure of lorazepam glucuronide in feline urine.
    • Both lorazepam and lorazepam glucuronide were detected in plasma.

    Conclusions:

    • Domestic cats effectively excrete lorazepam and its glucuronide conjugate.
    • This study provides conclusive evidence that cats utilize glucuronidation as a major pathway for xenobiotic metabolism.
    • The findings challenge previous notions of poor glucuronidation capacity in felines.

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