Aoyama T, Sasaki T, Kotaki H, Sawada Y, Sudoh Y, Honda Y, Iga T
Department of Pharmacy, University of Tokyo Hospital, Faculty of Medicine, Japan.
Clin Pharmacol Ther. 1994 Mar;55(3):270-6. doi: 10.1038/clpt.1994.27.
The pharmacokinetics of (+)-methylphenidate after oral administration of 20 mg racemic methylphenidate hydrochloride and the relationship between clinical effects of plasma (+)-methylphenidate concentration were investigated in 15 patients with hypersomnia and four healthy volunteers. The elimination half-life of (+)-methylphenidate in patients was within the range of 2.6 to 3 hours, and the time to reach the peak concentration ranged from 1 to 3 hours. The values of half-life and time to reach the peak concentration in the patients were almost the same as the values in healthy subjects. The plasma (+)-methylphenidate concentration profiles after repeated administration of racemic methylphenidate were similar to those after single administration. No correlation was observed between the plasma (+)-methylphenidate concentration and the subjective sleepiness as measured by Stanford Sleepiness Scale. On the other hand, a significant correlation was found between the sleep latency as measured by the multiple sleep latency test and the plasma concentrations of (+)-methylphenidate (r = 0.850). The time course of the sleep latency after repeated administration was similar to that after single administration. The sleep latency of more than 10 minutes was achieved by maintaining the plasma (+)-methylphenidate concentrations above 3 ng/ml.
在15名发作性睡病患者和4名健康志愿者中，研究了口服20毫克消旋盐酸哌甲酯后(+)-哌甲酯的药代动力学以及血浆(+)-哌甲酯浓度与临床疗效之间的关系。患者体内(+)-哌甲酯的消除半衰期在2.6至3小时范围内，达到峰值浓度的时间为1至3小时。患者的半衰期和达到峰值浓度的时间值与健康受试者的值几乎相同。重复给药消旋哌甲酯后的血浆(+)-哌甲酯浓度曲线与单次给药后相似。血浆(+)-哌甲酯浓度与通过斯坦福嗜睡量表测量的主观嗜睡程度之间未观察到相关性。另一方面，通过多次睡眠潜伏期试验测量的睡眠潜伏期与血浆(+)-哌甲酯浓度之间发现显著相关性（r = 0.850）。重复给药后睡眠潜伏期的时间进程与单次给药后相似。通过将血浆(+)-哌甲酯浓度维持在3 ng/ml以上可实现超过10分钟的睡眠潜伏期。
