Stereoselective toxicokinetics and tissue distribution of ethofumesate in rabbits.

Wentao Zhu, Ziheng Dang, Jing Qiu, Chunguang Lv, Guifang Jia, Li Li, Zhiqiang Zhou

Index: Chirality 19(8) , 632-7, (2007)

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Abstract

The stereoselective toxicokinetics of ethofumesate enantiomers following a single intravenous (i.v.) administration at doses of 30 mg/kg were investigated in rabbits. Plasma concentrations of (+)- and (-)-ethofumesate were analyzed by a validated chiral HPLC method that involved extraction of plasma with organic solvent followed by separation on a cellulose-Tris-(3,5-dimethylphenylcarbamate)-based chiral column and quantification by UV absorbance at 230 nm. Plasma concentration-time curves after i.v. administration were best described by an open two-compartment model. The concentration of the (-)-enantiomer decreased more rapidly than that of the (+)-enantiomer. Significant differences in toxicokinetic parameters between the two enantiomers indicated that stereoselective behavior occurred with the (-)-enantiomer being preferentially metabolized and eliminated.