Darwish Mona, Kirby Mary, Hellriegel Edward T
Clinical Pharmacology Department, Cephalon, Inc., Frazer, Pennsylvania 19355, USA.
Clin Drug Investig. 2009;29(9):601-12. doi: 10.2165/11317740-000000000-00000.
Armodafinil, the R- and longer-lasting isomer of modafinil, may maintain higher plasma drug concentrations compared with racemic modafinil because of stereospecific differences in elimination of its isomers. This analysis set out to compare the steady-state pharmacokinetic profiles of armodafinil and modafinil on a milligram-to-milligram basis following once-daily administration.
A post hoc analysis of two multiple-dose pharmacokinetic studies in healthy male subjects aged 18-50 years was conducted to compare dose-normalized (200 mg/day) plasma drug concentration and pharmacokinetic data for subjects in each study who completed 7 days of once-daily (morning) administration of armodafinil (n = 34) or modafinil (n = 18).
Dose-normalized plasma concentrations of armodafinil on day 7 were higher than those of modafinil, with the greatest differences being observed later in the day. Across the 24-hour dose interval, plasma drug concentration fluctuation and swing were 28% and 42% less, respectively, with armodafinil than with modafinil. In addition, average late-day (3 pm to 7 pm after an 8 am dosing) plasma drug concentrations and partial values for the area under the plasma concentration versus time curve for 7-11 hours after dosing were both 44% higher with armodafinil.
At steady state, armodafinil produces consistently higher plasma drug concentrations late in the day than modafinil when compared on a milligram-to-milligram basis. The distinct pharmacokinetic profile of armodafinil compared with that of the racemate may result in fundamentally different durations of action. These differences between the two medications cannot be made equivalent by increasing the dose of the racemate without introducing potential safety concerns.
阿莫达非尼是莫达非尼的R型且作用时间更长的异构体，由于其异构体消除存在立体特异性差异，与消旋莫达非尼相比，它可能维持更高的血浆药物浓度。本分析旨在比较每日一次给药后，阿莫达非尼和莫达非尼按毫克对毫克计算的稳态药代动力学特征。
对两项针对18 - 50岁健康男性受试者的多剂量药代动力学研究进行事后分析，以比较剂量标准化（200毫克/天）的血浆药物浓度以及每项研究中完成7天每日一次（早晨）服用阿莫达非尼（n = 34）或莫达非尼（n = 18）的受试者的药代动力学数据。
第7天阿莫达非尼的剂量标准化血浆浓度高于莫达非尼，在当天晚些时候差异最为明显。在24小时给药间隔内，阿莫达非尼的血浆药物浓度波动和摆动分别比莫达非尼低28%和42%。此外，阿莫达非尼给药后平均傍晚（上午8点给药后下午3点至7点）血浆药物浓度以及给药后7 - 11小时血浆浓度 - 时间曲线下面积的部分值均高出44%。
在稳态时，按毫克对毫克计算，阿莫达非尼在当天晚些时候产生的血浆药物浓度始终高于莫达非尼。与消旋体相比，阿莫达非尼独特的药代动力学特征可能导致作用持续时间存在根本差异。在不引入潜在安全问题的情况下，增加消旋体的剂量无法使这两种药物的差异等同。
