blood pressure. Serious rashes can develop in rare cases, and require immediate medical attention due to the possibility of Steven's-Johnson Syndrome, or other hypersensitivities to armodafinil. Pharmacology Pharmacodynamics The mechanism of action of armodafinil is unknown. Armodafinil (R-(−)-modafinil) has pharmacological properties almost identical to those of modafinil (a mixture of R-(−)- and (S)-(+)-modafinil). The (R)- and (S)-enantiomers have similar pharmacological action in animals. Armodafinil has wake-promoting actions similar to sympathomimetic agents including amphetamine and methylphenidate, although its pharmacologic profile is not identical to that of the sympathomimetic amines. Armodafinil is an indirect dopamine receptor agonist; it binds in vitro to the dopamine transporter (DAT) and inhibits dopamine reuptake. For modafinil, this activity has been associated in vivo with increased extracellular dopamine levels. In genetically engineered mice lacking the dopamine transporter, 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, an inhibitor of dopamine synthesis, blocks the action of amphetamine but does not block locomotor activity induced by modafinil. In addition to its wake-promoting effects and ability to increase locomotor activity in animals, according to Nuvigil prescribing information from manufacturer Cephalon, armodafinil produces psychoactive and euphoric effects, alterations in mood, perception, thinking, and feelings typical of other central nervous system (CNS) stimulants in humans. Armodafinil, like racemic modafinil, may also possess reinforcing properties, as evidenced by its self-administration in monkeys previously trained to administer cocaine; armodafinil was also partially discriminated as stimulant-like. A Cephalon-founded study in which patients were administered modafinil, methylphenidate, and a placebo found that modafinil produces "psychoactive and euphoric effects and feelings consistent with [methylphenidate]." Pharmacokinetics Armodafinil exhibits linear time-independent kinetics following single and multiple oral dose administration. Increase in systemic exposure is proportional over the dose range of 50–400 mg. No time-dependent change in kinetics was observed through 12 weeks of dosing. Apparent steady state for armodafinil was reached within 7 days of dosing. At steady state, the systemic exposure for armodafinil is 1.8 times the exposure observed after a single dose. The concentration-time profiles of the (R)-(−)-enantiomer following a single dose of 50 mg Nuvigil or 100 mg Provigil (modafinil being a 1:1 mixture of (R)-(−)- and (S)-(−)- enantiomers) are nearly superimposable. However, the Cmax of armodafinil at steady state was 37% higher following administration of 200 mg Nuvigil than the