Disposition of fenbendazole in cattle

Area of Science:

• Veterinary Pharmacology
• Drug Metabolism and Pharmacokinetics

Background:

• Fenbendazole (FBZ) is a widely used anthelmintic in cattle.
• Understanding its absorption, distribution, metabolism, and excretion (ADME) is crucial for effective treatment protocols.

Purpose of the Study:

• To characterize the plasma concentration-time profiles of FBZ and its metabolites after intravenous (IV) and oral administration in cattle.
• To quantify the total excretion of FBZ and its metabolites in urine and feces over a 6-day period.
• To identify the primary excretory products and assess oral bioavailability.

Main Methods:

• A crossover study design was employed, administering FBZ to cattle via IV and oral routes.
• Plasma concentrations of FBZ and its metabolites (oxfendazole, sulfone) were measured over time.
• Urine and fecal samples were collected for 6 days to determine total excretion of FBZ and metabolites.

Main Results:

• Plasma concentration-time profiles for FBZ, oxfendazole, and the sulfone were established for both administration routes.
• The major excretory product identified in urine and feces was p-hydroxyfenbendazole (FBZ-OH).
• Only 44.6% of the orally administered dose was eliminated within 6 days, suggesting significant sequestration, likely in the gastrointestinal tract.

Conclusions:

• Oral administration of FBZ in cattle results in limited systemic absorption and elimination.
• p-hydroxyfenbendazole (FBZ-OH) is the predominant metabolite excreted.
• A substantial portion of orally administered FBZ is sequestered, impacting its overall bioavailability.