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目的研究中国健康志愿者静脉滴注左旋奥硝唑剂量递增的耐受性、安全性及药动学。方法 20名健康男性、20名健康女性受试者按体重分层随机分入4组,分别接受500,1 000,1 250,1 500 mg单次用药试验;单次用药试验结束清洗2周后,500 mg剂量组再次接受每天早、晚500 mg连续5 d的多次用药试验;1 000 mg剂量组再次接受1 000 mg奥硝唑(阳性对照比较不良反应)的单次用药试验。观察不良事件,HPLC测定血浆中左旋奥硝唑浓度,BPSS2.0计算主要药动学参数。结果单次静脉滴注左旋奥硝唑500,1 000,1 250,1 500 mg的不良反应为0/9,0/10,0/10,2/10;多次静脉滴注左旋奥硝唑500 mg的不良反应为3/10;单次静脉滴注消旋奥硝唑1 000 mg的不良反应为5/10。单次用药500,1 000,1 500 mg,多次用药500 mg的ρmax分别是(8.63±2.57),(18.6±4.08),(27.5±10.6),(23.4±4.67)mg·L-1;AUC0-60分别为(109.5±24.0),(293.1±69.9),(422.9±84.0),(412.3±99.4)mg.h.L-1。结论中国健康志愿者静脉滴注左旋奥硝唑500～1 500 mg单剂量,500mg多剂量是安全,能够耐受的;500～1 500 mg内呈线性药动学特征,多次用药后体内有一定蓄积。
Objective To study the tolerability, safety and pharmacokinetics of intravenous infusion of levorotatory ornidazole in Chinese healthy volunteers. Methods Twenty healthy males and 20 healthy females were randomly divided into four groups according to body weight and received 500,1000,1 250,1 500 mg single-dose test respectively. After the single-dose test was finished for 2 weeks . The 500 mg dose group received multiple daily doses of 500 mg for 5 days each morning and evening. The 1 000 mg dose group once again received a single dose of 1 000 mg ornidazole (positive control). Adverse events were observed. HPLC was used to determine the concentration of levorotary ornidazole in plasma. BPSS2.0 was used to calculate the main pharmacokinetic parameters. Results A single intravenous infusion of ornithinol 500,1 000,1 250,1 500 mg adverse reactions to 0 / 9,0 / 10,0 / 10,2 / 10; multiple intravenous infusion of levorotatory ornidazole Adverse reactions to 500 mg were 3/10; a single intravenous injection of racemic ornidazole 1000 mg had a side effect of 5/10. The values of ρmax for single-dose 500,1 000,1 500 mg and multiple-dose 500 mg were (8.63 ± 2.57), (18.6 ± 4.08), (27.5 ± 10.6) and (23.4 ± 4.67) mg · L -1, respectively. AUC0-60 were (109.5 ± 24.0), (293.1 ± 69.9), (422.9 ± 84.0), (412.3 ± 99.4) mg.hL-1, respectively. Conclusions Chinese healthy volunteers can safely and tolerate 500 mg to 1 500 mg single dose of levonorideol or 500 mg to 1 500 mg intravenously, and have linear pharmacokinetic characteristics within 500 mg to 1 500 mg. After multiple injections, Certain accumulation.