AI Article Synopsis
- Fenofibrate, a PPARalpha agonist linked to cancer risk, shows species-specific metabolism, with new metabolites discovered in monkeys and rats, but not yet in beagle dogs.
- In a study, beagle dogs were given fenofibrate with their food, and urine and plasma samples were analyzed using advanced LC-MS/MS techniques.
- Seven new metabolites of fenofibrate were identified in beagle dogs, revealing that they metabolize the drug differently and produce more secondary metabolites than rats do.
Article Abstract
Fenofibrate is a prototypical agonist of peroxisome proliferator-activated receptor alpha (PPARalpha) which is well known to be associated with species related carcinogenesis. Important species differences have been reported in its metabolism and elimination pattern. Its new metabolites have been revealed in Cynomolgus monkeys and Sprague-Dawley rats. However in beagle dogs, several polar metabolites of fenofibrate have not been identified yet. In this study, beagle dogs were orally dosed with fenofibrate mixed with feeds. Urine and plasma samples were collected and subject to LC-MS/MS by comparison with authentic compounds and confirmed using an API 4000 Q-TRAP system. In vitro cultured primary hepatocytes were used to reveal metabolic pathways and confirm the data in vivo. Seven new metabolites of fenofibrate in dogs were identified, and their metabolic pathways were revealed. Fenofibrate in beagle dogs was found to be more prone to be metabolized into other secondary metabolites than fenofibric acid, compared with that in rats.
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