Abstract
The stereoselective metabolism of ethofumesate (ETO) and its enantiomers in rabbit and rat liver microsomes have been studied by chiral high-performance liquid chromatography (HPLC) method. Two metabolites were detected in both liver microsomes in the presence of β-nicotinamide adenine dinucleotide phosphate (NADPH).The T1/2 of (+)-ETO and (−)-ETO in rabbit liver microsomes were 12.2 and 4.7 min of rac-ETO and 25.9 and 6.7 of ETO enantiomers. However, the T1/2 of (+)-ETO and (−)-ETO in rat liver microsomes were 5.3 and 5.9 min of rac-ETO and 7.8 and 10.6 of ETO enantiomers. The stereoselective selectivity is similar to the in vivo study.After incubation of ETO enantiomers, stereoselectivity was present in the formation of ETO-OH enantiomer in rabbit liver microsomes, but stereoselectivity was not evident in rat liver microsomes.There was no chiral inversion from the (+)-ETO to (−)-ETO or inversion from (−)-ETO to (+)-ETO in both rabbit and rat liver microsomes.
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