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A Weil

Publications and source records attributed to A Weil.

75 records · Page 5Linked to original sources
PubMedDate not supplied

The metabolism and disposition of 14C-fenofibrate in human volunteers.

The metabolic fate of a single dose of 14C-fenofibrate has been studied in a panel of eight healthy volunteers (four males and four females). In 7 days, a total of 84% of the administered dose was recovered, with 59% in the urine and 25% in the feces. The majority of the urinary 14C was excreted within 24 hr, whereas the bulk of the fecal 14C was recovered over the first 3 days after dosing. The major urinary metabolite was the ester glucuronide of fenofibric acid, accompanied by much smaller amounts of fenofibric acid and the benzhydrol and its glucuronide. The principal compound in feces was unchanged fenofibrate, together with smaller quantities of fenofibric acid and polar unknown metabolite(s). Experiments on the stability of fenofibryl glucuronide showed it to be less reactive than most ester glucuronides.

Biotransformation↗
PubMedDate not supplied

The metabolism and disposition of fenofibrate in rat, guinea pig, and dog.

The metabolism and disposition of orally administered single doses of [14C]fenofibrate (isopropyl 2-[4-(4-chlorobenzoyl)phenoxy]-2- methylpropionate) have been studied in rat, guinea pig, and dog. In rats, the urinary excretion of 14C in 5 days varied from 11 to 51% of the dose and was markedly dependent upon the dose form given. The interpretation of these data in terms of factors affecting the absorption of fenofibrate from the gut is complicated by the enterohepatic recirculation of metabolites. The tissue distribution of 14C after oral administration of an ethanolic solution of fenofibrate has been studied in the rat. The only tissues in which the concentration of 14C exceeded that in the blood were the organs of absorption and elimination, the gut, liver, and kidneys. Guinea pigs excreted 53% of the dose in the urine in 5 days, with a further 34% in the feces, while in dogs the corresponding figures were 9% and 81%, respectively. In all three species, all the urinary metabolites were products of ester hydrolysis, and the principal excretion product was "reduced fenofibric acid" which arose by subsequent carbonyl reduction. Glucuronidation of fenofibric acid and "reduced fenofibric acid" was a very minor reaction in the rat and guinea pig and was not detected in the dog. In addition, polar unknown metabolite(s) were detected in all three species, but were not investigated further. The results are discussed in terms of the comparative disposition of fenofibrate and other hypolipidemic agents and the contribution of these findings to the safety assessment of such drugs.

Animals↗