Fenbendazole pharmacokinetics, metabolism, and potentiation in horses.

This research investigates the behavior of the drug fenbendazole in horses, exploring its absorption, metabolism, and excretion, as well as the impact of factors like feeding or coadministration with the metabolic inhibitor piperonyl-butoxide.

Background of the Research

• The primary aim of this study was to provide insights into the pharmacokinetics, metabolism, and intestinal elimination of fenbendazole (FBZ) and its oxidized form, fenbendazole sulphoxide (FBZSO), and their metabolites in horses.
• It aimed to understand the influence of feeding on the absorption of FBZ and observe the impact of the metabolic inhibitor, piperonyl-butoxide, on the metabolic processes of benzimidazoles, a class of organic compounds to which fenbendazole belongs.
• The researchers also assessed the effect of piperonyl-butoxide on the enantiomeric genesis or formation of the sulfoxide moiety (a specific chemical group).

Key Findings

• The researchers observed that after administering FBZ and FBZSO, the FBZ sulphone metabolite was most prevalent in the horses’ plasma.
• It was also noted that the ‘C(max)’ (The maximum (peak) serum concentration that a drug achieves) and ‘area under the plasma curve’ (AUC – a measure of the drug’s exposure to the body) values for each moiety were significantly larger following FBZSO than FBZ administration.
• In fecal matter, the administered parent molecule (either FBZ or FBZSO) was most plentiful.
• Crucially, the study indicated that the combined AUC for active benzimidazole moieties following oral administration of FBZ was almost 4 times higher in unfed horses than in fed horses, suggesting that the drug’s effectiveness may be impacted by the presence of food in the stomach.

Coadministration of Piperonyl-butoxide

• The data showed that the coadministration of piperonyl-butoxide significantly increased the ‘AUC’ and ‘C(max)’ of active moieties (potentially active parts of a drug molecule) following intravenous administration of FBZSO and oral administration of FBZ.
• Piperonyl-butoxide was seen to alter the ratio of FBZSO-1/FBZSO-2 enantiomers from >4:1 to 1:1, meaning it drastically affected the proportion of the two forms of sulfoxide moiety.

Conclusion of the Study

• The study concluded that in horses, the efficiency of FBZ and FBZSO could be improved by administering the drugs to unfed animals and coadministering with piperonyl-butoxide.
• These findings have potential implications for the use of FBZ and FBZSO in veterinary medicine and could inform more effective administration guidelines for these drugs in horses.