Institute of Antibiotics, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai 200040, China; Key Laboratory of Clinical Pharmacology of Antibiotics, National Health and Family Planning Commission, 12 Middle Wulumuqi Road, Shanghai 200040, China.
Institute of Antibiotics, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai 200040, China; Key Laboratory of Clinical Pharmacology of Antibiotics, National Health and Family Planning Commission, 12 Middle Wulumuqi Road, Shanghai 200040, China.
Int J Antimicrob Agents. 2016 Mar;47(3):224-8. doi: 10.1016/j.ijantimicag.2015.12.007. Epub 2016 Jan 21.
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 750mg every 24h (q24h) (test group, 12 subjects) versus 500mg every 12h (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 0-72h 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 750mg q24h in clinical practice, which shows a lower AR and similar safety compared with the conventional 500mg q12h regimen. [Chinese Clinical Trial Registry identifier: ChiCTR-IPR-14005574.].
左旋奥硝唑是奥硝唑的左旋异构体，与奥硝唑相比具有相似的抗厌氧活性和更低的中枢神经毒性。本研究为开放标签、平行、随机、多剂量试验，旨在比较健康中国志愿者中左旋奥硝唑静脉输注 750mg 每 24 小时（q24h）（试验组，12 例）和 500mg 每 12 小时（q12h）（对照组，12 例）连续 7 天的药代动力学和安全性。静脉输注 7 天后，与对照组相比，试验组的左旋奥硝唑蓄积比（AR）降低 33.8%，分布容积增加 45.0%。0-72 小时期间左旋奥硝唑的累积尿排泄率（Ae0-72）在试验组为 16.6±20.9%，在对照组为 24.2±5.7%。代谢物 M1/母药和 M4/母药的比值分别为试验组 2.18±0.77%和 2.94±0.37%，对照组为 3.15±1.09%和 3.18±0.34%。两组 M1、M2 和 M4 的 Ae0-72 均<10%。两种方案均耐受良好。药物相关不良事件通常为一过性，严重程度为轻度或中度。这些发现支持推荐临床实践中静脉输注左旋奥硝唑 750mg q24h，与常规 500mg q12h 方案相比，AR 较低且安全性相似。[中国临床试验注册中心标识符：ChiCTR-IPR-14005574。]。
