Enantioselective metabolism and enantiomerization of benalaxyl in mice

Chemosphere. 2017 Feb:169:308-315. doi: 10.1016/j.chemosphere.2016.11.091. Epub 2016 Nov 22.

Abstract

The enantiomerization and enantioselective metabolism of benalaxyl in mice after a single gavage administration were investigated in the present study. The pharmacokinetic result indicated that elimination of (-)-R-benalaxyl in plasma was slightly faster with the t1/2 of 26.65 h and 28.88 h for (-)-R- and (+)-S-benalaxyl, respectively. Consistent with this, elimination in tissues and excretion were also enantioselective, with (+)-S-benalaxyl enriched in all tissues, urine and feces. And formation of the metabolites also exhibited an enantioselective manner. Both benalaxyl and most of its metabolites exhibited a potent excretion to feces and urine. In addition, significant enantiomerization of benalaxyl enantiomers was observed in plasma, with a larger extent from R to S than S to R. Thus, this difference in enantiomerization may be one of the reasons to explain the enantioselective enrichment of (+)-S-benalaxyl in mice observed in this study. Data from this study proves that besides metabolic enzymes, enantiomerization could be another important factor that contributes to the enantioselective metabolism of a chiral pesticide. Thus, research at enantiomeric level is necessary for efficient risk assessment of chiral pesticides.

Keywords: Benalaxyl; Enantiomerization; Enantioselectivity; Metabolism; Mice.

MeSH terms

  • Alanine / analogs & derivatives*
  • Alanine / chemistry
  • Alanine / metabolism
  • Animals
  • Male
  • Mice
  • Pesticides / chemistry*
  • Stereoisomerism
  • Tissue Distribution

Substances

  • Pesticides
  • benalaxyl
  • Alanine