Wong Y N, King S P, Simcoe D, Gorman S, Laughton W, McCormick G C, Grebow P
Cephalon, Inc., West Chester, Pennsylvania, USA.
J Clin Pharmacol. 1999 Mar;39(3):281-8.
An open-label, single-center, single-dose, parallel-group study was performed in healthy young males and females as well as healthy elderly males to examine the influence of age and gender on the pharmacokinetics of modafinil following administration of a single 200 mg oral dose. Twelve subjects were enrolled in each of the following three groups: young males, young females, and elderly males. Each fasted (overnight) subject received 2 x 100 mg modafinil tablets. Blood and urine samples were collected at various times up to 72 hours postdose for the determination of plasma and urine levels of modafinil as well as the acid and sulfone metabolites. The plasma concentrations of the individual isomers, d- and l-modafinil, were also determined. Pharmacokinetic parameters were determined by noncompartmental methods. Modafinil was well tolerated at a single oral dose of 200 mg. The most commonly reported adverse events were headache, fever, pharyngitis, and asthenia. There were no clinically meaningful differences with respect to the incidence rate of treatment-emergent adverse events among the young female, young male, and old male groups. Modafinil was rapidly absorbed after oral dosing and slowly cleared (t1/2 approximately 11-14 hr) from the body. Modafinil acid was the major urinary metabolite, which accounted for 35% to 60% of the dose. Results from this study indicated that there were age and gender effects on modafinil clearance processes. In this regard, the clearance rate of modafinil in males decreased with age while young females cleared modafinil at a faster rate than young males. Stereospecific pharmacokinetics of modafinil were also demonstrated. The d-modafinil was eliminated three times faster than the l-modafinil.
在健康年轻男性和女性以及健康老年男性中进行了一项开放标签、单中心、单剂量、平行组研究，以考察年龄和性别对单次口服200 mg莫达非尼后其药代动力学的影响。以下三组每组招募了12名受试者：年轻男性、年轻女性和老年男性。每位空腹（过夜）受试者服用2片100 mg莫达非尼片剂。在给药后长达72小时的不同时间点采集血液和尿液样本，以测定血浆和尿液中莫达非尼及其酸和砜代谢物的水平。还测定了单个异构体d-和l-莫达非尼的血浆浓度。药代动力学参数采用非房室方法测定。莫达非尼单次口服200 mg时耐受性良好。最常报告的不良事件为头痛、发热、咽炎和乏力。年轻女性、年轻男性和老年男性组中治疗中出现的不良事件发生率在临床上无显著差异。莫达非尼口服给药后吸收迅速，从体内清除缓慢（半衰期约11 - 14小时）。莫达非尼酸是主要的尿液代谢物，占给药剂量的35%至60%。该研究结果表明，年龄和性别对莫达非尼的清除过程有影响。在这方面，男性中莫达非尼的清除率随年龄降低，而年轻女性清除莫达非尼的速度比年轻男性快。还证明了莫达非尼的立体特异性药代动力学。d-莫达非尼的消除速度比l-莫达非尼快三倍。
