title: Improved pharmacokinetic profile of levornidazole following intravenous infusion of 750mg every 24h compared with 500mg every 12h in healthy Chinese volunteers.
abstract: 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.].
authors.affiliation: 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.
authors.forename: Yuran
authors.initials: Y
authors.lastname: Cao
authors.affiliation: 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.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Yuancheng
authors.initials: Y
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Beining
authors.initials: B
authors.lastname: Guo
authors.affiliation: 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.
authors.forename: Jicheng
authors.initials: J
authors.lastname: Yu
authors.affiliation: 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.
authors.forename: Guoying
authors.initials: G
authors.lastname: Cao
authors.affiliation: 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. Electronic address: zhangj_fudan@aliyun.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Yaoguo
authors.initials: Y
authors.lastname: Shi
authors.affiliation: 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.
authors.forename: Yingyuan
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D000981:Antiprotozoal Agents / Q000493:pharmacokinetics*; D044466:Asian People; D002681:China; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009950:Ornidazole / Q000009:adverse effects* / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D000981:Antiprotozoal Agents; D009950:Ornidazole
keywords: Dosage regimen; Levornidazole; Metabolite; Pharmacokinetics; Safety