title: Metabolism of fenofibrate in beagle dogs: new metabolites identified and metabolic pathways revealed.
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.
authors.affiliation: Ningbo College of Health Sciences, Ningbo, PR China.
authors.forename: Julin
authors.initials: J
authors.lastname: Yang
authors.forename: Wenxia
authors.initials: W
authors.lastname: Luo
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Renke
authors.initials: R
authors.lastname: Dai
authors.forename: Aiming
authors.initials: A
authors.lastname: Liu
mesh_terms: D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D011345:Fenofibrate / Q000378:metabolism* / Q000493:pharmacokinetics; D022781:Hepatocytes / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000378:metabolism* / Q000493:pharmacokinetics; D007202:Indicators and Reagents; D013058:Mass Spectrometry; D053858:Metabolic Networks and Pathways; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000960:Hypolipidemic Agents; D007202:Indicators and Reagents; D011345:Fenofibrate