Effect of repeated doses of albendazole on enantiomerism of its sulfoxide metabolite in goats.
Five adult Saanen goats were dosed orally 3 times with albendazole (2.5 mg/kg of body weight) at 24-hour intervals, and blood samples were taken by jugular venapuncture at standardized intervals. Plasma was analyzed to determine concentrations of S-oxidation metabolites, and a chiral column was used for enantiomeric discrimination of the sulfoxide metabolite of albendazole. Marked changes were evident between the first and subsequent plasma profiles concerning, on one hand, the proportions of sulfoxide and sulfone metabolites concentrations and, on the other hand, the enantiomeric balance of sulfoxide metabolite. These correlated phenomena may be explained by the following arguments: the enzyme responsible for sulfoxidation is mainly a flavine-containing monooxygenase, whereas the enzyme responsible for sulfonation is a cytochrome-dependent monooxygenase; the latter, but not the former, is induced by albendazole; the enantioselectivities of both enzymic systems are opposite, the flavine produces the (+) sulfoxide, whereas the cytochromes can use as a substrate, specifically, the (-) sulfoxide.
Benoit
E
E
INRA-DGER Laboratory of Metabolic Toxicology, School of Veterinary Medicine of Lyon, Marcy l'Etoile, France.
Besse
S
S
Delatour
P
P
D015766:Albendazole / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D000871:Anthelmintics / Q000737:chemistry* / Q000493:pharmacokinetics; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006041:Goats / Q000378:metabolism*
D000871:Anthelmintics; D015766:Albendazole; C027186:albendazole sulfoxide