Stereoselective pharmacokinetics of diniconazole enantiomers in rabbits.
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.
Wang
Qiuxia
Q
Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing, China.
Qiu
Jing
J
Zhou
Zhiqiang
Z
Cao
Aocheng
A
Wang
Xinquan
X
Zhu
Wentao
W
Dang
Ziheng
Z
D000818:Animals; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D007275:Injections, Intravenous; D015394:Molecular Structure; D011817:Rabbits; D013237:Stereoisomerism; D014230:Triazoles / Q000737:chemistry / Q000493:pharmacokinetics*
D014230:Triazoles; C049346:diniconazole