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Stereoselective pharmacokinetics of diniconazole enantiomers in rabbits
Author(s) -
Wang Qiuxia,
Qiu Jing,
Zhou Zhiqiang,
Cao Aocheng,
Wang Xinquan,
Zhu Wentao,
Dang Ziheng
Publication year - 2009
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.20667
Subject(s) - chemistry , enantiomer , pharmacokinetics , stereoselectivity , triazole , chromatography , kinetics , high performance liquid chromatography , stereochemistry , pharmacology , organic chemistry , catalysis , medicine , physics , quantum mechanics
Diniconazole [( E )‐( RS )‐1‐(2,4,‐dichlorophenyl)‐4,4‐dimethyl‐2‐(1 H ‐1,2,4‐triazole‐1‐yl)pent‐1‐en‐3‐ol)] is a potent triazole fungicide. The enantioselective pharmacokinetics of diniconazole enantiomers in rabbits was studied via intravenous (i.v.) injection. The pharmacokinetics and the enantiomer fraction (EF) were determined using normal high‐performance liquid chromatography with diode array detection and a cellulose‐tris‐(3,5‐dimethylphenylcarbamate)‐based chiral stationary phase (CDMPC‐CSP). The time–concentration curves in plasma were fitted by a two‐compartment open mode. The results showed that the concentration of S ‐diniconazole in plasma decreased faster than that of R ‐diniconazole, and EFs increased with time after administration of racemic diniconazole ( rac ‐diniconazole). The R ‐/ S ‐enantiomer ratio of the area under the time–plasma concentration curve (AUC 0–∞ ) after administration was 1.52. The total plasma clearance value of S ‐enantiomer was 1.57‐fold higher than that of the R ‐diniconazole. These results indicate substantial stereoselectivity in the kinetics of diniconazole enantiomers in rabbit. Chirality, 2009. © 2008 Wiley‐Liss, Inc.