【科普】Modafinil与Ritalin 两种神秘的“聪明药”
Armodafinil说明书翻译42
Although the abuse potential of armodafinil has not been specifically studied, its abuse potential is likely to be similar to that of modafinil. In humans, modafinil produces psychoactive and euphoric effects, alterations in mood, perception, thinking and feelings typical of other CNS stimulants. In in vitro binding studies, modafinil binds to the dopamine reuptake site and causes an increase in extracellular dopamine, but no increase in dopamine release. Modafinil is reinforcing, as evidenced by its self-administration in monkeys previously trained to self-administer cocaine. In some studies, modafinil was also partially discriminated as stimulant-like. Physicians should follow patients closely, especially those with a history of drug and/or stimulant (e.g., methylphenidate, amphetamine, or cocaine) abuse. Patients should be observed for signs of misuse or abuse (e.g., incrementation of doses or drug-seeking behavior).
处方者应当心患者对Armodafinil的滥用。
在体外结合研究中，Modafinil通过与多巴胺再摄取位点结合引起细胞外多巴胺的增加，但多巴胺释放没有增加。
在部分nation，Modafinil被归类为兴奋剂。
医生应密切关注患者，特别是那些有药物或兴奋剂（如Ritalin、Amphetamine）滥用史的患者。
应观察患者的误用或滥用迹象（例如，剂量增加或寻求药物的行为）。
The abuse potential of modafinil (200, 400, and 800 mg) was assessed relative to methylphenidate (45 and 90 mg) in an inpatient study in individuals experienced with drugs of abuse. Results from this clinical study demonstrated that modafinil produced psychoactive and euphoric effects and feelings consistent with other scheduled CNS stimulants (methylphenidate).
在对滥用药物的个体的住院研究中，相对于哌醋甲酯（45和90mg）评估Modafinil（200,400和800mg）的滥用可能性。
该临床研究的结果表明，Modafinil产生了与其他预定的CNS兴奋剂（哌醋甲酯）一致的精神活性、欣快效果和感觉。
Although the abuse potential of armodafinil has not been specifically studied, its abuse potential is likely to be similar to that of modafinil. In humans, modafinil produces psychoactive and euphoric effects, alterations in mood, perception, thinking and feelings typical of other CNS stimulants. In in vitro binding studies, modafinil binds to the dopamine reuptake site and causes an increase in extracellular dopamine, but no increase in dopamine release. Modafinil is reinforcing, as evidenced by its self-administration in monkeys previously trained to self-administer cocaine. In some studies, modafinil was also partially discriminated as stimulant-like. Physicians should follow patients closely, especially those with a history of drug and/or stimulant (e.g., methylphenidate, amphetamine, or cocaine) abuse. Patients should be observed for signs of misuse or abuse (e.g., incrementation of doses or drug-seeking behavior).
处方者应当心患者对Armodafinil的滥用。
在体外结合研究中，Modafinil通过与多巴胺再摄取位点结合引起细胞外多巴胺的增加，但多巴胺释放没有增加。
在部分nation，Modafinil被归类为兴奋剂。
医生应密切关注患者，特别是那些有药物或兴奋剂（如Ritalin、Amphetamine）滥用史的患者。
应观察患者的误用或滥用迹象（例如，剂量增加或寻求药物的行为）。
The abuse potential of modafinil (200, 400, and 800 mg) was assessed relative to methylphenidate (45 and 90 mg) in an inpatient study in individuals experienced with drugs of abuse. Results from this clinical study demonstrated that modafinil produced psychoactive and euphoric effects and feelings consistent with other scheduled CNS stimulants (methylphenidate).
在对滥用药物的个体的住院研究中，相对于哌醋甲酯（45和90mg）评估Modafinil（200,400和800mg）的滥用可能性。
该临床研究的结果表明，Modafinil产生了与其他预定的CNS兴奋剂（哌醋甲酯）一致的精神活性、欣快效果和感觉。
Armodafinil说明书翻译43
Pregnancy & lactation
Armodafinil should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during therapy. Patients should be cautioned regarding the potential increased risk of pregnancy when using steroidal contraceptives (including depot or implantable contraceptives) with armodafinil tablets and for one month after discontinuation of therapy.
怀孕和哺乳期
只有潜在的益处大于对胎儿的潜在风险时，才应在怀孕期间使用Armodafinil。
建议患者在治疗期间怀孕或打算怀孕时通知医生。
当使用Armodafinil和停止治疗后一个月内使用甾体避孕药（包括长效制剂或植入式避孕药）时，应警告患者可能增加怀孕风险。
Pregnancy & lactation
Armodafinil should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during therapy. Patients should be cautioned regarding the potential increased risk of pregnancy when using steroidal contraceptives (including depot or implantable contraceptives) with armodafinil tablets and for one month after discontinuation of therapy.
怀孕和哺乳期
只有潜在的益处大于对胎儿的潜在风险时，才应在怀孕期间使用Armodafinil。
建议患者在治疗期间怀孕或打算怀孕时通知医生。
当使用Armodafinil和停止治疗后一个月内使用甾体避孕药（包括长效制剂或植入式避孕药）时，应警告患者可能增加怀孕风险。
Armodafinil说明书翻译44
The effect of armodafinil on labor and delivery in humans has not been systematically investigated.
Armodafinil对人类分娩的影响尚未得到系统研究。
It is not known whether armodafinil or its metabolites are excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when armodafinil tablets are administered to a nursing woman.
目前尚不清楚Armodafinil或其代谢产物是否在人乳中出现。
由于许多药物在人乳中出现，因此当给予哺乳期妇女Armodafinil时应谨慎行事。
The effect of armodafinil on labor and delivery in humans has not been systematically investigated.
Armodafinil对人类分娩的影响尚未得到系统研究。
It is not known whether armodafinil or its metabolites are excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when armodafinil tablets are administered to a nursing woman.
目前尚不清楚Armodafinil或其代谢产物是否在人乳中出现。
由于许多药物在人乳中出现，因此当给予哺乳期妇女Armodafinil时应谨慎行事。
Armodafinil说明书翻译45
Drug interactions:
Due to the partial involvement of CYP3A enzymes in the metabolic elimination of armodafinil, coadministration of potent inducers of CYP3A4/5 (e.g., carbamazepine, phenobarbital, rifampin) or inhibitors of CYP3A4/5 (e.g., ketoconazole, erythromycin) could alter the plasma levels of armodafinil.
药物相互作用：
由于CYP3A酶部分参与Armodafinil的代谢消除，因此CYP3A4/5的强效诱导剂（如卡马西平，苯巴比妥，利福平）或CYP3A4/5抑制剂（如酮康唑，红霉素）可改变Armodafinil的血药浓度。
Drug interactions:
Due to the partial involvement of CYP3A enzymes in the metabolic elimination of armodafinil, coadministration of potent inducers of CYP3A4/5 (e.g., carbamazepine, phenobarbital, rifampin) or inhibitors of CYP3A4/5 (e.g., ketoconazole, erythromycin) could alter the plasma levels of armodafinil.
药物相互作用：
由于CYP3A酶部分参与Armodafinil的代谢消除，因此CYP3A4/5的强效诱导剂（如卡马西平，苯巴比妥，利福平）或CYP3A4/5抑制剂（如酮康唑，红霉素）可改变Armodafinil的血药浓度。
Armodafinil说明书翻译46
In vitro data demonstrated that armodafinil shows a weak inductive response for CYP1A2 and possibly CYP3A activities in a concentration related manner and demonstrated that CYP2C19 activity is reversibly inhibited by armodafinil. However, the effect on CYP1A2 activity was not observed clinically in an interaction study performed with caffeine.
体外实验数据表明，Armodafinil是CYP1A2的弱诱导剂，并证明Armodafinil可抑制CYP2C19酶的活性。 然而，在用咖啡因进行的相互作用研究中，临床上未观察到Armodafinil对CYP1A2活性的影响。
注：在下英语水平有限，对这段的翻译可能不是很正确。如有错误，欢迎大家纠正。
In vitro data demonstrated that armodafinil shows a weak inductive response for CYP1A2 and possibly CYP3A activities in a concentration related manner and demonstrated that CYP2C19 activity is reversibly inhibited by armodafinil. However, the effect on CYP1A2 activity was not observed clinically in an interaction study performed with caffeine.
体外实验数据表明，Armodafinil是CYP1A2的弱诱导剂，并证明Armodafinil可抑制CYP2C19酶的活性。 然而，在用咖啡因进行的相互作用研究中，临床上未观察到Armodafinil对CYP1A2活性的影响。
注：在下英语水平有限，对这段的翻译可能不是很正确。如有错误，欢迎大家纠正。
Armodafinil说明书翻译49
Data specific to armodafinil drug-drug interaction potential with CNS active drugs are not available. However, the following available drug-drug interaction information on modafinil should be applicable to armodafinil.
Modafinil与Armodafinil相似，因此下列与Modafinil有关的情况适用于Armodafinil。
Concomitant administration of modafinil with methylphenidate, or dextroamphetamine produced no significant alterations on the pharmacokinetic profile of modafinil or either stimulant, even though the absorption of modafinil was delayed for approximately one hour.
同时给予Modafinil与哌醋甲酯或右旋安非他明，对Modafinil或任一刺激剂的药代动力学特征没有显著改变，即使莫达非尼的吸收延迟约1小时。
Concomitant modafinil or clomipramine did not alter the pharmacokinetic profile of either drug; however, one incident of increased levels of clomipramine and its active metabolite desmethylclomipramine was reported in a patient with narcolepsy during treatment with modafinil.
同时使用Modafinil或氯米帕明不会改变任何一种药物的药代动力学特征;
然而，在用Modafinil治疗嗜睡症的患者中出现了一例氯丙咪嗪及其活性代谢物去甲基环丙咪嗪水平升高的事件。
Data specific to armodafinil drug-drug interaction potential with monoamine oxidase (MAO) inhibitors are not available. Therefore, caution should be used when concomitantly administering MAO inhibitors and armodafinil tablets.
没有单胺氧化酶（MAO）抑制剂与Armodafinil相互作用的数据。 因此，MAO抑制剂和Modafinil同时使用时应谨慎使用。
Data specific to armodafinil drug-drug interaction potential for additional other drugs are not available. However, the available drug-drug interaction information on modafinil should be applicable to armodafinil. Concomitant administration of modafinil with warfarin did not produce significant changes in the pharmacokinetic profiles of R- and S-warfarin. However, since only a single dose of warfarin was tested in this study, a pharmacodynamic interaction cannot be ruled out. Therefore, more frequent monitoring of prothrombin times/INR should be considered whenever armodafinil tablets is coadministered with warfarin.
Modafinil与华法林的同时给药时并未出现药代动力学特征的显著变化。
然而，由于在该研究中仅测试了单剂量的华法林，因此不能排除药效学相互作用。
Side effects:
The most common adverse events reported by >=5% of patients on armodafinil treatment include headache, nausea, dizziness and insomnia.
副作用：
最常见的副作用包括头痛，恶心，头晕和失眠，出现率>=5%。
The adverse events observed with armodafinil in > 1% of patients were palpitations, diarrhea, dry mouth, dyspepsia, upper abdominal pain, constipation, vomiting, loose stools, fatigue, thirst, influenza like illness, pain, pyrexia, seasonal allergy, increased gamma-glutamyltransferase, increased heart rate, anorexia, decreased appetite, disturbance in attention, tremor, migraine, paraesthesia, anxiety, depression, agitation, nervousness, depressed mood, polyuria, dyspnea, rash, contact, dermatitis, hyperhydrosis etc.
不常见的副作用有心悸，腹泻，口干，消化不良，上腹痛，便秘，呕吐，稀便，疲劳，口渴，疼痛，发热，心率加快，厌食，食欲减退，注意力受到干扰，震颤，偏头痛，感觉异常，焦虑，抑郁，情绪激动，神经过敏，情绪低落，多尿，呼吸困难，皮疹，皮炎，多汗等，出现率>1%。
Data specific to armodafinil drug-drug interaction potential with CNS active drugs are not available. However, the following available drug-drug interaction information on modafinil should be applicable to armodafinil.
Modafinil与Armodafinil相似，因此下列与Modafinil有关的情况适用于Armodafinil。
Concomitant administration of modafinil with methylphenidate, or dextroamphetamine produced no significant alterations on the pharmacokinetic profile of modafinil or either stimulant, even though the absorption of modafinil was delayed for approximately one hour.
同时给予Modafinil与哌醋甲酯或右旋安非他明，对Modafinil或任一刺激剂的药代动力学特征没有显著改变，即使莫达非尼的吸收延迟约1小时。
Concomitant modafinil or clomipramine did not alter the pharmacokinetic profile of either drug; however, one incident of increased levels of clomipramine and its active metabolite desmethylclomipramine was reported in a patient with narcolepsy during treatment with modafinil.
同时使用Modafinil或氯米帕明不会改变任何一种药物的药代动力学特征;
然而，在用Modafinil治疗嗜睡症的患者中出现了一例氯丙咪嗪及其活性代谢物去甲基环丙咪嗪水平升高的事件。
Data specific to armodafinil drug-drug interaction potential with monoamine oxidase (MAO) inhibitors are not available. Therefore, caution should be used when concomitantly administering MAO inhibitors and armodafinil tablets.
没有单胺氧化酶（MAO）抑制剂与Armodafinil相互作用的数据。 因此，MAO抑制剂和Modafinil同时使用时应谨慎使用。
Data specific to armodafinil drug-drug interaction potential for additional other drugs are not available. However, the available drug-drug interaction information on modafinil should be applicable to armodafinil. Concomitant administration of modafinil with warfarin did not produce significant changes in the pharmacokinetic profiles of R- and S-warfarin. However, since only a single dose of warfarin was tested in this study, a pharmacodynamic interaction cannot be ruled out. Therefore, more frequent monitoring of prothrombin times/INR should be considered whenever armodafinil tablets is coadministered with warfarin.
Modafinil与华法林的同时给药时并未出现药代动力学特征的显著变化。
然而，由于在该研究中仅测试了单剂量的华法林，因此不能排除药效学相互作用。
Side effects:
The most common adverse events reported by >=5% of patients on armodafinil treatment include headache, nausea, dizziness and insomnia.
副作用：
最常见的副作用包括头痛，恶心，头晕和失眠，出现率>=5%。
The adverse events observed with armodafinil in > 1% of patients were palpitations, diarrhea, dry mouth, dyspepsia, upper abdominal pain, constipation, vomiting, loose stools, fatigue, thirst, influenza like illness, pain, pyrexia, seasonal allergy, increased gamma-glutamyltransferase, increased heart rate, anorexia, decreased appetite, disturbance in attention, tremor, migraine, paraesthesia, anxiety, depression, agitation, nervousness, depressed mood, polyuria, dyspnea, rash, contact, dermatitis, hyperhydrosis etc.
不常见的副作用有心悸，腹泻，口干，消化不良，上腹痛，便秘，呕吐，稀便，疲劳，口渴，疼痛，发热，心率加快，厌食，食欲减退，注意力受到干扰，震颤，偏头痛，感觉异常，焦虑，抑郁，情绪激动，神经过敏，情绪低落，多尿，呼吸困难，皮疹，皮炎，多汗等，出现率>1%。
Armodafinil说明书翻译50
Overdosage:
There were no overdoses reported in the clinical studies of armodafinil tablets.
药物过量：
在Armodafinil的临床研究中没有报道过量服用。
Overdosage:
There were no overdoses reported in the clinical studies of armodafinil tablets.
药物过量：
在Armodafinil的临床研究中没有报道过量服用。
Armodafinil说明书翻译51
Symptoms of armodafinil tablets overdose are likely to be similar to those of modafinil. Overdose in modafinil clinical trials included excitation or agitation, insomnia, and slight or moderate elevations in hemodynamic parameters. From post-marketing experience with modafinil, there have been no reports of fatal overdoses involving modafinil alone (doses up to 12 grams). Overdoses involving multiple drugs, including modafinil, have resulted in fatal outcomes. Symptoms most often accompanying modafinil overdose, alone or in combination with other drugs have included; insomnia; central nervous system symptoms such as restlessness, disorientation, confusion, excitation and hallucination; digestive changes such as nausea and diarrhea; and cardiovascular changes such as tachycardia, bradycardia, hypertension and chest pain.
Armodafinil过量时出现的症状可能与Modafinil相似。 Modafinil过量服用的症状包括兴奋或激动，失眠以及血液动力学参数轻微或中度升高。
从Modafinil上市后的经验来看，没有关于单独使用Modafinil过量致死的报告（最高剂量高达12克）。
有涉及多种药物（包括Modafinil）过量服用导致致命的报道。
Modafinil过量症状包括失眠，中枢神经系统症状，如烦躁不安，迷失方向，精神错乱，兴奋和幻觉，恶心和腹泻等消化系统改变，和心血管改变，如心动过速，心动过缓，高血压和胸痛。
Symptoms of armodafinil tablets overdose are likely to be similar to those of modafinil. Overdose in modafinil clinical trials included excitation or agitation, insomnia, and slight or moderate elevations in hemodynamic parameters. From post-marketing experience with modafinil, there have been no reports of fatal overdoses involving modafinil alone (doses up to 12 grams). Overdoses involving multiple drugs, including modafinil, have resulted in fatal outcomes. Symptoms most often accompanying modafinil overdose, alone or in combination with other drugs have included; insomnia; central nervous system symptoms such as restlessness, disorientation, confusion, excitation and hallucination; digestive changes such as nausea and diarrhea; and cardiovascular changes such as tachycardia, bradycardia, hypertension and chest pain.
Armodafinil过量时出现的症状可能与Modafinil相似。 Modafinil过量服用的症状包括兴奋或激动，失眠以及血液动力学参数轻微或中度升高。
从Modafinil上市后的经验来看，没有关于单独使用Modafinil过量致死的报告（最高剂量高达12克）。
有涉及多种药物（包括Modafinil）过量服用导致致命的报道。
Modafinil过量症状包括失眠，中枢神经系统症状，如烦躁不安，迷失方向，精神错乱，兴奋和幻觉，恶心和腹泻等消化系统改变，和心血管改变，如心动过速，心动过缓，高血压和胸痛。
Armodafinil说明书翻译52
No specific antidote exists for the toxic effects of armodafinil tablet overdose. Such overdoses should be managed with primarily supportive care, including cardiovascular monitoring. If there are no contraindications, induced emesis or gastric lavage should be considered. There are no data to suggest the utility of dialysis or urinary acidification or alkalinization in enhancing drug elimination.
Armodafinil过量的毒性作用没有特定的解毒剂。
过量用药应该进行支持性护理，包括心血管监测。
如果没有禁忌症，应考虑诱发呕吐或洗胃。
没有数据表明透析有清除药物的作用。
No specific antidote exists for the toxic effects of armodafinil tablet overdose. Such overdoses should be managed with primarily supportive care, including cardiovascular monitoring. If there are no contraindications, induced emesis or gastric lavage should be considered. There are no data to suggest the utility of dialysis or urinary acidification or alkalinization in enhancing drug elimination.
Armodafinil过量的毒性作用没有特定的解毒剂。
过量用药应该进行支持性护理，包括心血管监测。
如果没有禁忌症，应考虑诱发呕吐或洗胃。
没有数据表明透析有清除药物的作用。
Armodafinil说明书翻译53
Clinical Pharmacology:
Armodafinil is a wakefulness promoting agent.
临床药理学：
Armodafinil是一种觉醒促进剂。
Mechanism of Action
The precise mechanisms through which armodafinil (R-enantiomer) or modafinil (mixture of R- and S-enantiomers) promote wakefulness is unknown. Both armodafinil and modafinil have shown similar pharmacological properties in nonclinical and in vitro studies, to the extent tested.
作用机制
Armodafinil（R-对映体）或Modafinil（R-和S-对映体的混合物）促进觉醒的机制尚不清楚。
Armodafinil和Modafinil在非临床和体外研究中显示出相似的药理学性质。
Clinical Pharmacology:
Armodafinil is a wakefulness promoting agent.
临床药理学：
Armodafinil是一种觉醒促进剂。
Mechanism of Action
The precise mechanisms through which armodafinil (R-enantiomer) or modafinil (mixture of R- and S-enantiomers) promote wakefulness is unknown. Both armodafinil and modafinil have shown similar pharmacological properties in nonclinical and in vitro studies, to the extent tested.
作用机制
Armodafinil（R-对映体）或Modafinil（R-和S-对映体的混合物）促进觉醒的机制尚不清楚。
Armodafinil和Modafinil在非临床和体外研究中显示出相似的药理学性质。
Armodafinil说明书翻译54
Armodafinil is not a direct- or indirect-acting dopamine receptor agonist. However, in vitro, both armodafinil and modafinil bind to the dopamine transporter and inhibit dopamine reuptake. For modafinil, this activity has been associated in vivo with increased extracellular dopamine levels in some brain regions of animals. In genetically engineered mice lacking the dopamine transporter (DAT), modafinil lacked wake-promoting activity, suggesting that this activity was DAT-dependent. However, the wake-promoting effects of modafinil, unlike those of amphetamine, were not antagonized by the dopamine receptor antagonist haloperidol in rats. In addition, alpha-methyl-p-tyrosine, a dopamine synthesis inhibitor, blocks the action of amphetamine, but does not block locomotor activity induced by modafinil.
Armodafinil不是直接或间接作用的多巴胺受体激动剂。
然而，在体外，Armodafinil和Modafinil都与多巴胺转运蛋白结合并抑制多巴胺再摄取。
对于Modafinil，这种活性在体内与动物的一些脑区域中的细胞外多巴胺水平增加有关。
在缺乏多巴胺转运蛋白（DAT）的基因工程小鼠中，Modafinil作用下降，表明该活性是DAT依赖性的。
然而，与安非他明不同，Modafinil的唤醒作用不会被大鼠中的多巴胺受体拮抗剂氟哌啶醇拮抗。
此外，多巴胺合成抑制剂α-甲基-p-酪氨酸阻断苯丙胺的作用，但不阻断Modafinil诱导的运动活动。
Armodafinil is not a direct- or indirect-acting dopamine receptor agonist. However, in vitro, both armodafinil and modafinil bind to the dopamine transporter and inhibit dopamine reuptake. For modafinil, this activity has been associated in vivo with increased extracellular dopamine levels in some brain regions of animals. In genetically engineered mice lacking the dopamine transporter (DAT), modafinil lacked wake-promoting activity, suggesting that this activity was DAT-dependent. However, the wake-promoting effects of modafinil, unlike those of amphetamine, were not antagonized by the dopamine receptor antagonist haloperidol in rats. In addition, alpha-methyl-p-tyrosine, a dopamine synthesis inhibitor, blocks the action of amphetamine, but does not block locomotor activity induced by modafinil.
Armodafinil不是直接或间接作用的多巴胺受体激动剂。
然而，在体外，Armodafinil和Modafinil都与多巴胺转运蛋白结合并抑制多巴胺再摄取。
对于Modafinil，这种活性在体内与动物的一些脑区域中的细胞外多巴胺水平增加有关。
在缺乏多巴胺转运蛋白（DAT）的基因工程小鼠中，Modafinil作用下降，表明该活性是DAT依赖性的。
然而，与安非他明不同，Modafinil的唤醒作用不会被大鼠中的多巴胺受体拮抗剂氟哌啶醇拮抗。
此外，多巴胺合成抑制剂α-甲基-p-酪氨酸阻断苯丙胺的作用，但不阻断Modafinil诱导的运动活动。
Armodafinil说明书翻译55
Armodafinil and modafinil have wake-promoting actions similar to sympathomimetic agents including amphetamine and methylphenidate, although their pharmacologic profile is not identical to that of the sympathomimetic amines. In addition to its wake-promoting effects and ability to increase locomotor activity in animals, modafinil produces psychoactive and euphoric effects, alterations is mood, perception, thinking and feelings typical of other CNS stimulants in humans.
Armodafinil和Modafinil具有类似于拟交感神经药物（包括苯丙胺和哌甲酯）的促觉醒作用，尽管它们的药理学特征与拟交感神经胺的药理学特征不同。
除了其促进觉醒作用和增加动物运动活动的能力之外，Modafinil还产生精神活性和欣快效果，改变人的情绪、感知、思维和感觉。
Based on nonclinical studies, two major metabolites, acid and sulfone, of modafinil or armodafinil, do not appear to contribute to the CNS activating properties of the parent compounds.
Modafinil和Armodafinil的两种主要代谢物Modafinil酸和Modafinil砜没有生理活性。
Armodafinil and modafinil have wake-promoting actions similar to sympathomimetic agents including amphetamine and methylphenidate, although their pharmacologic profile is not identical to that of the sympathomimetic amines. In addition to its wake-promoting effects and ability to increase locomotor activity in animals, modafinil produces psychoactive and euphoric effects, alterations is mood, perception, thinking and feelings typical of other CNS stimulants in humans.
Armodafinil和Modafinil具有类似于拟交感神经药物（包括苯丙胺和哌甲酯）的促觉醒作用，尽管它们的药理学特征与拟交感神经胺的药理学特征不同。
除了其促进觉醒作用和增加动物运动活动的能力之外，Modafinil还产生精神活性和欣快效果，改变人的情绪、感知、思维和感觉。
Based on nonclinical studies, two major metabolites, acid and sulfone, of modafinil or armodafinil, do not appear to contribute to the CNS activating properties of the parent compounds.
Modafinil和Armodafinil的两种主要代谢物Modafinil酸和Modafinil砜没有生理活性。
Armodafinil说明书翻译56
Pharmacokinetics
The active component of armodafinil tablets is armodafinil, which is the longer-lived enantiomer of modafinil. Armodafinil tablets exhibits linear time independent kinetics following single and multiple oral dose administration. Increase in systemic exposure is proportional over the dose range of 50 to 400 mg. No time dependent change in kinetics was observed through 12 weeks of dosing. At steady state, the systemic exposure for armodafinil tablets is 1.8 times the exposure observed after a single dose. The concentration-time profiles of the pure R-enantiomer following administration of 50 mg armodafinil tablets or 100 mg modafinil are nearly superimposable.
药代动力学
Armodafinil片剂的活性成分是Armodafinil，它是Modafinil的长寿命对映体。
Armodafinil片剂在单次和多次口服给药后表现出与线性时间无关的动力学。
全身暴露的增加与剂量范围成正比。
在给药12周后没有观察到动力学的时间依赖性变化。
在稳定状态下，Armodafinil片剂的全身暴露是单次剂量后观察到的暴露的1.8倍。
给予50mgArmodafinil片剂或100mgModafinil后，纯R-对映体的浓度 - 时间曲线几乎是可叠加的。
Pharmacokinetics
The active component of armodafinil tablets is armodafinil, which is the longer-lived enantiomer of modafinil. Armodafinil tablets exhibits linear time independent kinetics following single and multiple oral dose administration. Increase in systemic exposure is proportional over the dose range of 50 to 400 mg. No time dependent change in kinetics was observed through 12 weeks of dosing. At steady state, the systemic exposure for armodafinil tablets is 1.8 times the exposure observed after a single dose. The concentration-time profiles of the pure R-enantiomer following administration of 50 mg armodafinil tablets or 100 mg modafinil are nearly superimposable.
药代动力学
Armodafinil片剂的活性成分是Armodafinil，它是Modafinil的长寿命对映体。
Armodafinil片剂在单次和多次口服给药后表现出与线性时间无关的动力学。
全身暴露的增加与剂量范围成正比。
在给药12周后没有观察到动力学的时间依赖性变化。
在稳定状态下，Armodafinil片剂的全身暴露是单次剂量后观察到的暴露的1.8倍。
给予50mgArmodafinil片剂或100mgModafinil后，纯R-对映体的浓度 - 时间曲线几乎是可叠加的。
Armodafinil说明书翻译57
Armodafinil is readily absorbed after oral administration. The absolute oral bioavailability was not determined due to the aqueous insolubility of armodafinil, which precluded intravenous administration. Peak plasma concentrations are attained at approximately 2 hours in the fasted state. Food effect on the overall bioavailability of armodafinil tablets is considered minimal; however, time to reach peak concentration (tmax) may be delayed by approximately 2-4 hours in the fed state. Since the delay in tmax is also associated with elevated plasma levels later in time, food can potentially affect the onset and time course of pharmacologic action for armodafinil tablets.
口服给药后，Armodafinil较易被吸收。
绝对口服生物利用率未确定，因为Armodafinil的水不溶性，所以不能通过静脉注射给药。
在空腹状态下服药约2小时后血药浓度达到峰值。
食物对Armodafinil总生物利用度的影响很小；
然而，在饱腹状态下，血药浓度达到峰值的时间（tmax）会延迟约2-4小时。
由于tmax的延迟还与后期血浆水平升高有关，因此食物可能潜在地影响Armodafinil的药理作用的开始时间和过程。
Armodafinil is readily absorbed after oral administration. The absolute oral bioavailability was not determined due to the aqueous insolubility of armodafinil, which precluded intravenous administration. Peak plasma concentrations are attained at approximately 2 hours in the fasted state. Food effect on the overall bioavailability of armodafinil tablets is considered minimal; however, time to reach peak concentration (tmax) may be delayed by approximately 2-4 hours in the fed state. Since the delay in tmax is also associated with elevated plasma levels later in time, food can potentially affect the onset and time course of pharmacologic action for armodafinil tablets.
口服给药后，Armodafinil较易被吸收。
绝对口服生物利用率未确定，因为Armodafinil的水不溶性，所以不能通过静脉注射给药。
在空腹状态下服药约2小时后血药浓度达到峰值。
食物对Armodafinil总生物利用度的影响很小；
然而，在饱腹状态下，血药浓度达到峰值的时间（tmax）会延迟约2-4小时。
由于tmax的延迟还与后期血浆水平升高有关，因此食物可能潜在地影响Armodafinil的药理作用的开始时间和过程。
Armodafinil说明书翻译58
Armodafinil has an apparent volume of distribution of approximately 42 L. Data specific to armodafinil protein binding are not available. However, modafinil is moderately bound to plasma protein (approximately 60%), mainly to albumin. The potential for interactions of armodafinil tablets with highly protein bound drugs is considered to be minimal.
Modafinil与血浆蛋白中度结合（约60％），主要与白蛋白结合。
Armodafinil与高蛋白结合药物发生相互作用的可能性很小。
In vitro and in vivo data show that armodafinil undergoes hydrolytic deamidation, S- oxidation, and aromatic ring hydroxylation, with subsequent glucuronide conjugation of the hydroxylated products. Amide hydrolysis is the single most prominent metabolic pathway, with sulfone formation by cytochrome P450 (CYP) 3A4/5 being next in importance. The other oxidative products are formed too slowly in vitro to enable identification of the enzyme(s) responsible. Only two metabolites reach appreciable concentrations in plasma (i.e., R-modafinil acid and modafinil sulfone).
体外和体内实验数据显示Armodafinil经历水解脱酰胺，S-氧化和芳环羟基化，随后羟基化产物的葡糖苷酸结合。
酰胺水解是最主要的代谢途径，细胞色素P450（CYP）3A4/5的砜形成是次要的。
其它氧化产物在体外形成得速度太慢，无法确定所负责的酶。
只有两种代谢物会在血浆中达到可观的浓度（即R-Modafinil酸和Modafinil砜）。
Armodafinil has an apparent volume of distribution of approximately 42 L. Data specific to armodafinil protein binding are not available. However, modafinil is moderately bound to plasma protein (approximately 60%), mainly to albumin. The potential for interactions of armodafinil tablets with highly protein bound drugs is considered to be minimal.
Modafinil与血浆蛋白中度结合（约60％），主要与白蛋白结合。
Armodafinil与高蛋白结合药物发生相互作用的可能性很小。
In vitro and in vivo data show that armodafinil undergoes hydrolytic deamidation, S- oxidation, and aromatic ring hydroxylation, with subsequent glucuronide conjugation of the hydroxylated products. Amide hydrolysis is the single most prominent metabolic pathway, with sulfone formation by cytochrome P450 (CYP) 3A4/5 being next in importance. The other oxidative products are formed too slowly in vitro to enable identification of the enzyme(s) responsible. Only two metabolites reach appreciable concentrations in plasma (i.e., R-modafinil acid and modafinil sulfone).
体外和体内实验数据显示Armodafinil经历水解脱酰胺，S-氧化和芳环羟基化，随后羟基化产物的葡糖苷酸结合。
酰胺水解是最主要的代谢途径，细胞色素P450（CYP）3A4/5的砜形成是次要的。
其它氧化产物在体外形成得速度太慢，无法确定所负责的酶。
只有两种代谢物会在血浆中达到可观的浓度（即R-Modafinil酸和Modafinil砜）。
Armodafinil说明书翻译59
Data specific to armodafinil disposition are not available. However, modafinil is mainly eliminated via metabolism, predominantly in the liver, with less than 10% of the parent compound excreted in the urine. A total of 81% of the administered radioactivity was recovered in 11 days post dose, predominantly in the urine (80% vs. 1.0% in the feces).
Modafinil主要通过代谢消除，主要是在肝脏中，少于10％的原药在尿液中排出。
在给药后11天内，总计81％的药物被回收，主要是在尿液中（尿液中为80％，粪便中为1.0％）。
Data specific to armodafinil disposition are not available. However, modafinil is mainly eliminated via metabolism, predominantly in the liver, with less than 10% of the parent compound excreted in the urine. A total of 81% of the administered radioactivity was recovered in 11 days post dose, predominantly in the urine (80% vs. 1.0% in the feces).
Modafinil主要通过代谢消除，主要是在肝脏中，少于10％的原药在尿液中排出。
在给药后11天内，总计81％的药物被回收，主要是在尿液中（尿液中为80％，粪便中为1.0％）。
Armodafinil说明书翻译60
After oral administration of armodafinil tablets, armodafinil exhibits an apparent monoexponential decline from the peak plasma concentration. The apparent terminal t 1/2 is approximately 15 hours. The oral clearance or armodafinil tablets is approximately 33 mL/min.
Armodafinil半衰期约为15小时。
After oral administration of armodafinil tablets, armodafinil exhibits an apparent monoexponential decline from the peak plasma concentration. The apparent terminal t 1/2 is approximately 15 hours. The oral clearance or armodafinil tablets is approximately 33 mL/min.
Armodafinil半衰期约为15小时。
Armodafinil说明书翻译61
The existence of multiple pathways for armodafinil metabolism, as well as the fact that a non-CYP-related pathway is the most rapid in metabolizing armodafinil, suggest that there is a low probability of substantive effects on the overall pharmacokinetic profile of armodafinil tablets due to CYP inhibition by concomitant medications.
Armodafinil在体内有多种代谢途径。
注：读不懂，大概是这个意思吧。
The existence of multiple pathways for armodafinil metabolism, as well as the fact that a non-CYP-related pathway is the most rapid in metabolizing armodafinil, suggest that there is a low probability of substantive effects on the overall pharmacokinetic profile of armodafinil tablets due to CYP inhibition by concomitant medications.
Armodafinil在体内有多种代谢途径。
注：读不懂，大概是这个意思吧。
Armodafinil说明书翻译62
In vitro data demonstrated that armodafinil shows a weak inductive response for CYP1A2 and possibly CYP3A activities in a concentration-related manner and that CYP2C19 activity is reversibly inhibited by armodafinil. Other CYP activities did not appear to be affected by armodafinil. An in vitro study demonstrated that armodafinil is a substrate of P-glycoprotein.
体外实验证明，Armodafinil是CYP1A2的弱诱导剂，并可抑制CYP2C19的活性。
其它CYP活性不受Armodafinil影响。
体外实验证明，Armodafinil是P-糖蛋白的底物。
In vitro data demonstrated that armodafinil shows a weak inductive response for CYP1A2 and possibly CYP3A activities in a concentration-related manner and that CYP2C19 activity is reversibly inhibited by armodafinil. Other CYP activities did not appear to be affected by armodafinil. An in vitro study demonstrated that armodafinil is a substrate of P-glycoprotein.
体外实验证明，Armodafinil是CYP1A2的弱诱导剂，并可抑制CYP2C19的活性。
其它CYP活性不受Armodafinil影响。
体外实验证明，Armodafinil是P-糖蛋白的底物。
Armodafinil说明书翻译66
In a single dose 200 mg modafinil study, severe chronic renal failure (creatinine clearance<=20 mL/min) did not significantly influence the pharmacokinetics of modafinil, but exposure to modafinil acid was increased 9-fold.
在200mgModafinil实验中，严重的慢性肾功能衰竭（肌酐清除率<= 20 mL / min）对Modafinil的药代动力学没有显著影响，但是其代谢产物Modafinil酸的暴露增加了9倍。
In a single dose 200 mg modafinil study, severe chronic renal failure (creatinine clearance<=20 mL/min) did not significantly influence the pharmacokinetics of modafinil, but exposure to modafinil acid was increased 9-fold.
在200mgModafinil实验中，严重的慢性肾功能衰竭（肌酐清除率<= 20 mL / min）对Modafinil的药代动力学没有显著影响，但是其代谢产物Modafinil酸的暴露增加了9倍。