Darwish Mona, Kirby Mary, Hellriegel Edward T, Robertson Philmore
Clinical Pharmacology Department, Cephalon, Inc., Frazer, Pennsylvania 19355, USA.
Clin Drug Investig. 2009;29(9):613-23. doi: 10.2165/11315280-000000000-00000.
Armodafinil, a non-amphetamine, wakefulness-promoting medication, is the R- and longer-lasting isomer of racemic modafinil. Armodafinil has been shown to improve wakefulness in patients with excessive sleepiness (ES) associated with treated obstructive sleep apnoea, shift work disorder or narcolepsy. In comparison with modafinil, armodafinil maintains higher plasma concentrations later in the day in healthy subjects. The objective of this analysis was to characterize the pharmacokinetic parameters related to those higher concentrations.
Data from three randomized studies in healthy adult subjects receiving single doses of either armodafinil (50, 100, 200, 250, 300 or 400 mg) or modafinil (400 mg) were pooled, and subsequently dose-normalized to a 200 mg dose for each drug. Non-compartmental pharmacokinetic parameters were assessed.
Armodafinil and modafinil both had a mean single-dose terminal elimination half-life of approximately 13 hours, with similar mean maximum plasma drug concentration (C(max)) and median time to C(max) values. After reaching C(max), plasma concentrations appeared to decline in a monophasic manner with armodafinil, but in a biphasic manner with modafinil due to the initial rapid elimination of its S-isomer. As a result, mean area under the plasma drug concentration versus time curve (AUC) from time zero to the time of the last measurable concentration (AUC(last)) and AUC from time zero to infinity (AUC(infinity)) values were 33% and 40% higher, respectively, with armodafinil compared with modafinil on a milligram-to-milligram basis.
Despite similar half-lives, plasma concentrations following armodafinil administration are higher late in the day than those following modafinil administration on a milligram-to-milligram basis. The different pharmacokinetic profile of armodafinil may result in improved wakefulness throughout the day in patients with ES compared with modafinil.
阿莫达非尼是一种非苯丙胺类促觉醒药物，是消旋莫达非尼的R型且作用时间更长的异构体。已证明阿莫达非尼可改善与经治疗的阻塞性睡眠呼吸暂停、倒班工作障碍或发作性睡病相关的过度嗜睡（ES）患者的觉醒状态。与莫达非尼相比，阿莫达非尼在健康受试者一天中较晚时候维持更高的血浆浓度。本分析的目的是描述与这些更高浓度相关的药代动力学参数。
汇总来自三项针对健康成年受试者的随机研究的数据，这些受试者接受单剂量的阿莫达非尼（50、100、200、250、300或400毫克）或莫达非尼（400毫克），随后将每种药物的剂量标准化为200毫克剂量。评估非房室药代动力学参数。
阿莫达非尼和莫达非尼的单剂量平均终末消除半衰期均约为13小时，平均最大血浆药物浓度（C(max)）和达峰时间中位数相似。达到C(max)后，阿莫达非尼的血浆浓度呈单相下降，而莫达非尼由于其S异构体的初始快速消除呈双相下降。因此，以毫克为基础，阿莫达非尼的血浆药物浓度-时间曲线下从时间零到最后可测量浓度的时间（AUC(last)）和从时间零到无穷大的AUC（AUC(infinity)）值分别比莫达非尼高33%和40%。
尽管半衰期相似，但以毫克为基础，服用阿莫达非尼后一天中较晚时候的血浆浓度高于服用莫达非尼后的血浆浓度。与莫达非尼相比，阿莫达非尼不同的药代动力学特征可能导致ES患者全天觉醒状态改善。
