Stereoselective Pharmacokinetics of Diniconazole Enantiomers in Rabbits

作者：Wang Qiuxia^*; Qiu Jing; Zhou Zhiqiang; Cao Aocheng; Wang Xinquan; Zhu Wentao; Dang Ziheng

来源：Chirality, 2009, 21(7): 699-703.

DOI：10.1002/chir.20667

• stereoselectivity
• diniconazole
• pharmacokinetics
• rabbit

Diniconazole [(E)-(RS)-1-(2,4,-dichlorophenyl)-4,4-dimethyl-2-(1H-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-infinity)) 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 21:69.9-703, 2009.

• 出版日期2009-7
• 单位中国农业科学院; 浙江省农业科学院; 中国农业大学; 中国农业科学院农业质量标准与检测技术研究所