title: Stereoselective kinetic study of hexaconazole enantiomers in the rabbit.
abstract: Hexaconazole [(RS)-2-(2,4-dichlorophenyl)-1-(1H-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-infinity)) 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.
authors.affiliation: Department of Applied Chemistry, China Agricultural University, Beijing 100094, China.
authors.forename: Qiu Xia
authors.initials: QX
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Qiu
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Gui Fang
authors.initials: GF
authors.lastname: Jia
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.forename: Jun Ling
authors.initials: JL
authors.lastname: Li
authors.forename: Zhi Qiang
authors.initials: ZQ
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D008401:Gas Chromatography-Mass Spectrometry; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects; D007700:Kinetics; D008099:Liver / Q000187:drug effects; D015394:Molecular Structure; D011817:Rabbits; D013237:Stereoisomerism; D014230:Triazoles / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*
chemical_list: D014230:Triazoles; C409722:hexaconazole