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Stereoselective kinetic study of hexaconazole enantiomers in the rabbit
Author(s) -
Wang Qiu Xia,
Qiu Jing,
Wang Ping,
Jia Gui Fang,
Wang Peng,
Li Jun Ling,
Zhou Zhi Qiang
Publication year - 2005
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.20152
Subject(s) - hexaconazole , chemistry , enantiomer , stereoselectivity , pharmacokinetics , chromatography , high performance liquid chromatography , pharmacology , stereochemistry , fungicide , biochemistry , catalysis , medicine , botany , carbendazim , biology
Hexaconazole [( RS )‐2‐(2,4‐dichlorophenyl)‐1‐(1 H ‐1,2,4‐triazol‐1‐yl)hexan‐2‐ol] is a potent triazole fungicide. The (−) isomer accounts for most of the fungicidal activity. The stereo‐ and/or enantioselective kinetics of hexaconazole were investigated in rabbits by intravenous injection. The concentrations of (−)‐ and (+)‐hexaconazole in plasma, liver, and kidney tissue were determined by HPLC with a cellulose tris(3,5‐dimethylphenylcarbamate)‐based chiral stationary phase and by gas chromatography–mass spectrometry. After intravenous administration of racemic hexaconazole ( rac ‐hexaconazole) at 30 mg/kg, plasma, liver, and kidney levels of the (+)‐enantiomer decreased more rapidly than those of the (−)‐enantiomer. The (−)‐/(+)‐enantiomer ratio of the area under the concentration–time curve (AUC 0–∞ ) was 1.35. The total plasma clearance value (CL) of (+)‐enantiomer was more than 1.3‐fold higher than that of the (−)‐hexaconazole. The enantiomeric ratio (ER) increased with time in plasma, liver, and kidney. Other pharmacokinetic parameters of the enantiomers were also different. These results indicate substantial stereoselectivity in the kinetics of hexaconazole enantiomers in rabbits. Chirality 17:186–192, 2005. © 2005 Wiley‐Liss, Inc.