Misumi J, Nagano M, Futatsuka M, Zhao W, Kudo M
Department of Public Health and Hygiene, Oita Medical University, Japan.
Neurochem Res. 1997 Jan;22(1):27-32. doi: 10.1023/a:1027317002386.
The same total dose (1.2 g/kg/week) of 2,5-hexanedione (2,5-HD) was administered subcutaneously at 100 mg/kg/12 hr, 200 mg/kg/24 hr, and 400 mg/kg/48 hr to three groups of Donryu rats. The peripheral neuropathy induced by 2,5-HD was confirmed by clinical observation every day, and neurophysiological measurements every 4 weeks. During the 15th week of this experiment, 2,5-HD concentrations in plasma 0.5 to 24 hours after injection were determined. It was found that the greater the dose of 2,5-HD per treatment injected, the earlier peripheral neuropathy developed. Toxicokinetic analysis showed that both the values of the area under the plasma concentration versus time curve and the half life of 2,5-HD were increased, but the excretion parameters (Ke) were decreased, in animals treated with 200 mg/kg/24 hr and 400 mg/kg/48 hr 2,5-HD.
将相同总剂量（1.2 g/kg/周）的2,5 -己二酮（2,5 - HD）以100 mg/kg/12小时、200 mg/kg/24小时和400 mg/kg/48小时的剂量分别皮下注射给三组东京大鼠。每天通过临床观察以及每4周通过神经生理学测量来确认由2,5 - HD诱导的周围神经病变。在该实验的第15周，测定注射后0.5至24小时血浆中的2,5 - HD浓度。结果发现，每次注射的2,5 - HD剂量越大，周围神经病变出现得越早。毒代动力学分析表明，在接受200 mg/kg/24小时和400 mg/kg/48小时2,5 - HD治疗的动物中，血浆浓度 - 时间曲线下面积值和2,5 - HD的半衰期均增加，但排泄参数（Ke）降低。
