title: Stereoselective pharmacokinetics of ornidazole after intravenous administration of individual enantiomers and the racemate.
abstract: The pharmacokinetics of ornidazole (ONZ) were investigated following i.v. administration of racemic mixture and individual enantiomers in beagle dogs. Plasma concentrations of ONZ enantiomers were analyzed by chiral high-performance liquid chromatography (HPLC) on a Chiralcel OB-H column with quantification by UV at 310 nm. Notably, the mean plasma levels of (-)-ONZ were higher in the elimination phase than those of (+)-ONZ. (-)-ONZ also exhibited greater t1/2, MRT, AUC(0-t) and smaller CL, than those of its antipode. The area under the plasma concentration-time curve (AUC(0-t)) of (-)-ONZ was about 1.2 times as high as that of (+)-ONZ. (+)-ONZ total body clearance (CL) was 1.4 times than its optical antipode. When given separately, there were significant differences in the values of AUC(0-infinity) and CL between ONZ enantiomers (P < 0.05), indicating that elimination of (+)-ONZ was more rapid than that of (-)-ONZ. No significant differences were found between the estimates of the pharmacokinetic parameters of (+)-ONZ or (-)-ONZ, obtained following administration as the individual and as a racemic mixture. This study demonstrates that the elimination of ONZ enantiomers is stereoselective and chiral inversion and enantiomer/enantiomer interaction do not occur when the enantiomers are given separately and as racemic mixture.
authors.affiliation: Key Laboratory of Drug Metabolism & Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Xiao Quan
authors.initials: XQ
authors.lastname: Liu
authors.forename: Jiao
authors.initials: J
authors.lastname: Zhong
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhao
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Wang
authors.forename: Guangji
authors.initials: G
authors.lastname: Wang
mesh_terms: D000818:Animals; D004285:Dogs; D007275:Injections, Intravenous; D015394:Molecular Structure; D009950:Ornidazole / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D013237:Stereoisomerism
chemical_list: D009950:Ornidazole