Wong Y N, King S P, Laughton W B, McCormick G C, Grebow P E
Cephalon, Inc., West Chester, PA 19380, USA.
J Clin Pharmacol. 1998 Mar;38(3):276-82. doi: 10.1002/j.1552-4604.1998.tb04425.x.
Modafinil is a novel wake-promoting agent being developed for treatment of excessive daytime sleepiness associated with narcolepsy. An open, 3 x 3 Latin square, randomized, cross-over study was performed in healthy males to compare the pharmacokinetics of single-dose oral modafinil (200 mg) and methylphenidate (40 mg) administered alone or in combination. Blood samples were obtained for analysis of d- and l-threo-methylphenidate and modafinil and its acid and sulfone metabolites. Pharmacokinetic parameters were determined by noncompartmental methods, but could not be evaluated for modafinil sulfone due to plasma levels that were close to the assay quantitation limit. Although sporadic differences in plasma concentrations were observed between treatments, coadministration of modafinil and methylphenidate did not significantly alter the plasma concentrations of modafinil, modafinil acid, modafinil sulfone, or methylphenidate enantiomers compared with administration of these agents alone. Half-life (t1/2), maximum concentration (Cmax), area under the concentration-time curve (AUC0-infinity), total clearance (Cl/F), and apparent volume of distribution (Vd/F) for modafinil and t1/2, Cmax, and AUC0-infinity for modafinil acid were not affected by concomitant administration of methylphenidate. Small but statistically significant increases in time to Cmax (tmax) were observed for modafinil and modafinil acid after methylphenidate coadministration compared with modafinil alone. Modafinil coadministration did not significantly alter the pharmacokinetics of d- or l-threo-methylphenidate, except for a small decrease in Vd/F of l-threo-methylphenidate. Concomitant methylphenidate may cause a delay in the oral absorption of modafinil, but this delay might not be relevant clinically. Coadministration did not alter the extent of oral absorption and disposition of either agent. Therefore, a pharmacokinetic interaction between modafinil and methylphenidate would be unlikely.
莫达非尼是一种新型促醒药物，正在研发用于治疗发作性睡病相关的日间过度嗜睡。在健康男性中进行了一项开放、3×3拉丁方、随机、交叉研究，以比较单剂量口服莫达非尼（200mg）和哌甲酯（40mg）单独给药或联合给药的药代动力学。采集血样分析d-和l-苏式哌甲酯以及莫达非尼及其酸和砜代谢物。药代动力学参数通过非房室方法测定，但由于血浆水平接近分析定量限，无法对莫达非尼砜进行评估。尽管在各治疗组间观察到血浆浓度存在散在差异，但与单独给药相比，莫达非尼和哌甲酯联合给药并未显著改变莫达非尼、莫达非尼酸、莫达非尼砜或哌甲酯对映体的血浆浓度。莫达非尼的半衰期（t1/2）、最大浓度（Cmax）、浓度-时间曲线下面积（AUC0-∞）、总清除率（Cl/F）和表观分布容积（Vd/F）以及莫达非尼酸的t1/2、Cmax和AUC0-∞不受哌甲酯联合给药的影响。与单独使用莫达非尼相比，哌甲酯联合给药后，莫达非尼和莫达非尼酸的达峰时间（tmax）出现了小幅度但具有统计学意义的延长。莫达非尼联合给药除使l-苏式哌甲酯的Vd/F略有降低外，并未显著改变d-或l-苏式哌甲酯的药代动力学。联合使用哌甲酯可能会导致莫达非尼口服吸收延迟，但这种延迟在临床上可能无关紧要。联合给药并未改变两种药物的口服吸收程度和处置过程。因此，莫达非尼和哌甲酯之间不太可能存在药代动力学相互作用。
