Improved pharmacokinetic profile of levornidazole following intravenous infusion of 750 mg every 24 h compared with 500 mg every 12 h in healthy Chinese volunteers

•2 levornidazole regimens were compared by pharmacokinetics and safety in subjects.•Levornidazole 750 mg q24h showed a lower accumulation ratio than 500 mg q12h.•Both regimens had a good safety profile without serious adverse events.•Levornidazole 750 mg q24h can be an effective treatment alternative to 500 mg q12h.

Levornidazole is the levo-isomer of ornidazole with similar anti-anaerobic activity and lower central neurotoxicity compared with ornidazole. This open-label, parallel, randomised, multidose trial was conducted to compare the pharmacokinetics and safety of levornidazole following intravenous (i.v.) infusion 750 mg every 24 h (q24h) (test group, 12 subjects) versus 500 mg every 12 h (q12h) (reference group, 12 subjects) for 7 days in healthy Chinese volunteers. Following i.v. infusion for 7 days, the test group showed a 33.8% lower accumulation ratio (AR) and a 45.0% higher volume of distribution of levornidazole than the reference group. The cumulative urinary excretion rate of levornidazole during the 0–72 h period (Ae0–72) was 16.6 ± 20.9% in the test group and 24.2 ± 5.7% in the reference group. The metabolite M1/parent and M4/parent ratios were, respectively, 2.18 ± 0.77% and 2.94 ± 0.37% in test group and 3.15 ± 1.09% and 3.18 ± 0.34% in the reference group. The Ae0–72 of M1, M2 and M4 were all <10% in both groups. Both regimens were well tolerated. Drug-related adverse events were generally transient and were mild or moderate in severity. These findings support the recommendation of i.v. infusion of levornidazole 750 mg q24h in clinical practice, which shows a lower AR and similar safety compared with the conventional 500 mg q12h regimen. [Chinese Clinical Trial Registry identifier: ChiCTR-IPR-14005574.]