title: Stereoselective pharmacokinetics of diniconazole enantiomers in rabbits.
abstract: 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.
authors.affiliation: Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing, China.
authors.forename: Qiuxia
authors.initials: Q
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Qiu
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zhou
authors.forename: Aocheng
authors.initials: A
authors.lastname: Cao
authors.forename: Xinquan
authors.initials: X
authors.lastname: Wang
authors.forename: Wentao
authors.initials: W
authors.lastname: Zhu
authors.forename: Ziheng
authors.initials: Z
authors.lastname: Dang
mesh_terms: 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*
chemical_list: D014230:Triazoles; C049346:diniconazole