Species differences for stereoselective metabolism of ethofumesate and its enantiomers in vitro

Abstract

1. 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).

2. The T_1/2 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 T_1/2 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.

3. 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.

4. There was no chiral inversion from the (+)-ETO to (−)-ETO or inversion from (−)-ETO to (+)-ETO in both rabbit and rat liver microsomes.

Keywords::

• Ethofumesate
• liver microsomes
• stereoselective metabolism
• rabbit
• rat

Acknowledgements

This work was funded by the National Natural Science Foundation of China (Grant Number 20477057).

Declaration of interest: The authors report no conflicts of interest.