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Xenobiotica; the fate of foreign compounds in biological systems

Stereoselective degradation of metalaxyl and its enantiomers in rat and rabbit hepatic microsomes in vitro.


PMID 22348420

Abstract

The stereoselective degradations of racemate metalaxyl (rac-MX) and its single enantiomers in rat and rabbit hepatic microsomes were assayed by a chiral high-performance liquid chromatography method. The t(1/2) of (+)-S-MX in rat liver microsomes was between 7-8 min tested by rac-MX and the individual (+)-S-enantiomer, respectively, and that for (-)-R-MX was 15-16 min. In contrast, t(1/2) in rabbit liver microsomes was much longer and showed great difference when using racemate and single enantiomer, which was similar to the results of in vivo study. The enantioselectivity in rat hepatic microsomes was more evident and the degradations of MX enantiomers in rat and rabbit hepatic microsomes were Nicotinamide adenine dinucleotide phosphate-dependent. Michaelis constant (K(m)) and intrinsic metabolic clearance (CL(int)) of (+)-S-MX were larger than that of (-)-R-MX and there was no chiral inversion from (+)-S-MX to (-)-R-MX or vice versa in both rat and rabbit hepatic microsomes.

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