Stereoselective kinetic study of hexaconazole enantiomers in the rabbit.
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.
Wang
Qiu Xia
QX
Department of Applied Chemistry, China Agricultural University, Beijing 100094, China.
Qiu
Jing
J
Wang
Ping
P
Jia
Gui Fang
GF
Wang
Peng
P
Li
Jun Ling
JL
Zhou
Zhi Qiang
ZQ
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*
D014230:Triazoles; C409722:hexaconazole