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Stereospecific biotransformation of albendazole in mouflon and rat‐isolated hepatocytes
Author(s) -
Velík J.,
Baliharová V.,
Skálová L.,
Szotáková B.,
Wsól V.,
Lamka J.
Publication year - 2003
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1046/j.1365-2885.2003.00484.x
Subject(s) - albendazole , enantiomer , stereospecificity , biotransformation , chemistry , anthelmintic , stereochemistry , substrate (aquarium) , sulfoxide , stereoselectivity , chromatography , biology , biochemistry , enzyme , organic chemistry , ecology , catalysis
The anthelmintic albendazole (ABZ) undergoes a two‐step oxidation resulting first in the formation of chiral albendazole sulfoxide (ABZSO) followed by its transformation to albendazole sulfone (ABZSO 2 ) in many farm and laboratory animal species. Although cloven‐hoofed game are also treated with ABZ, limited information concerning ABZ biotransformation in these species is available. The present study focused on in vitro ABZ sulfoxidation in hepatocytes from wild sheep‐mouflon ( Ovis musimon ) and comparison of ABZ sulfoxidation in mouflon and rat ( Rattus norvergicus ) hepatocytes. ABZ was used as a substrate for primary cultures of mouflon and rat hepatocytes. Time‐dependent stereospecific consumption of ABZSO and ABZSO 2 formation has been investigated. The metabolites were determined by high‐performance liquid chromatography with both achiral and chiral stationary phases. Although total‐ABZSO formation did not significantly differ between mouflon and rat, after separation of the (+)‐ABZSO and (−)‐ABZSO enantiomers a significant difference between species was found. The enantiomeric ratio of (+)/(−)‐ABZSO in mouflon hepatocytes was 2.8–3.8, while rat hepatocytes biotransformed ABZ to almost racemic ABZSO, with an enantiomeric ratio of 1.0–1.1. The ratio were similar for two concentrations of substrate used and stable over several time intervals. The formation of ABZSO 2 was more extensive in rat (approximately five times) than in mouflon hepatocytes.