Stereoselective toxicokinetics and tissue distribution of ethofumesate in rabbits |
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Authors: | Zhu Wentao Dang Ziheng Qiu Jing Lv Chunguang Jia Guifang Li Li Zhou Zhiqiang |
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Institution: | Department of Applied Chemistry, China Agricultural University, Beijing, People's Republic of China. |
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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. |
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