Pharmacokinetics and safety of injected ornidazole compared to its enantiomer levornidazole in healthy Chinese subjects.

OBJECTIVE: To compare the pharmacokinetics of levornidazole and ornidazole in healthy Chinese subjects after a single intravenous injection, and to determine whether the chiral inversion of levornidazole occurs in vivo.

MATERIALS AND METHODS: The study was a randomized, open-label, two-period crossover, single-dose design. A total of 12 subjects were enrolled in this study. Subjects received an intravenous injection of either levornidazole sodium chloride injection (200 mL: 0.5 g) or ornidazole sodium chloride injection (200 mL: 0.5 g) once per period. The plasma concentrations of levornidazole, ornidazole, and their metabolites were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Phenix WinNolin software (version 6.4) was used to calculate the pharmacokinetic parameters of levornidazole, ornidazole, and their metabolites.

RESULTS: Dexornidazole was not detected in the plasma or urine. After a single intravenous injection of levornidazole or ornidazole, there was no significant difference in Cmax between the two drugs (p < 0.05). The AUC0-∞ and AUC0-t of levornidazole were slightly lower than those of ornidazole. Metabolites M1 and M4 were detected in the plasma of both drugs, and their pharmacokinetic parameters were similar. Metabolites M1, M2, and M4 were present in urine. The average cumulative urinary excretion rates of levornidazole and its metabolites M1 and M4 were: during 0 - 24 hours (8.14 ± 0.80%, 0.560 ± 0.072%, and 1.42 ± 0.19%) and 0 - 60 hours (10.5 ± 1.0%, 0.960 ± 0.084%, and 2.52 ± 0.20%), the average cumulative urinary excretion rates of ornidazole and its metabolites M1 and M4 were: 0 - 24 hours (8.64 ± 0.98%, 0.486 ± 0.074%, and 1.46 ± 0.21%), 0 - 60 hours (11.8 ± 1.0%, 0.888 ± 0.070%, and 2.76 ± 0.20%). The incidence of adverse reactions was similar between the two drugs.

CONCLUSION: No chiral inversion of levornidazole occurred in vivo after intravenous administration of levornidazole. The pharmacokinetic parameters and cumulative excretion rates of levornidazole and ornidazole were similar. The safety results were basically consistent between the two drugs.