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 highโperformance liquid chromatography (HPLC) on a Chiralcel OBโH column with quantification by UV at 310 nm. Notably, the mean plasma levels of (โ)โONZ were higher in the elimination phase than those of (+)โONZ. (โ)โONZ also exhibited greater t~1/~~2~, MRT, AUC~0โt~ and smaller CL, than those of its antipode. The area under the plasma concentrationโtime curve (AUC~0โt~) of (โ)โONZ was about 1.2 times as high as that of (+)โONZ. (+)โONZ total body clearance (CL) was 1.4 times than its optical antipode. When given separately, there were significant differences in the values of AUC~0โ~~โ~ and CL between ONZ enantiomers (P < 0.05), indicating that elimination of (+)โONZ was more rapid than that of (โ)โONZ. No significant differences were found between the estimates of the pharmacokinetic parameters of (+)โONZ or (โ)โONZ, 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. Chirality, 2006. ยฉ 2006 WileyโLiss, Inc.