Stereoselective pharmacokinetics of ornidazole after intravenous administration of individual enantiomers and the racemate |
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Authors: | Chen Yan Liu Xiao Quan Zhong Jiao Zhao Xiaoping Wang Yongsheng Wang Guangji |
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Affiliation: | Key Laboratory of Drug Metabolism & Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, People's Republic of China. |
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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. |
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Keywords: | stereoselective pharmacokinetics chiral high‐performance liquid chromatography analysis rac‐ONZ (+)‐ONZ (−)‐ONZ |
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