BACKGROUND: Armodafinil (Nuvigil(®), Cephalon, Inc., Frazer, PA, USA), the 
longer-lasting isomer of racemic modafinil, is a nonamphetamine, 
wakefulness-promoting medication. In patients with excessive sleepiness 
associated with shift work disorder, treated obstructive sleep apnoea, or 
narcolepsy, armodafinil has been found to improve wakefulness throughout the 
shift or day. In addition, while not approved for this indication, armodafinil 
has been found to improve excessive sleepiness associated with jet-lag disorder.
OBJECTIVE: This study evaluated systemic exposure to armodafinil and its two 
major circulating metabolites, R-modafinil acid and modafinil sulfone, and 
assessed the tolerability profile of armodafinil in elderly and young subjects.
METHODS: The pharmacokinetics and tolerability of armodafinil were assessed in 
an open-label, multiple-dose, parallel-group study in two groups (n = 25 in each 
group) of healthy men (elderly group aged ≥65 years and young group aged 18-45 
years) who received armodafinil 50 mg on day 1, 100 mg on day 2 and 150 mg once 
daily on days 3 through 7. Plasma concentrations of armodafinil and its 
metabolites were quantified over 72 hours following the last dose on day 7. 
Pharmacokinetic parameters, including area under the plasma drug 
concentration-versus-time curve during a dosing interval (AUC(τ)) and maximum 
observed plasma drug concentration (C(max)), and tolerability were assessed.
RESULTS: All 50 subjects enrolled in the study were evaluable for tolerability 
and 49 were included in the pharmacokinetic analysis. One elderly subject was 
excluded from the pharmacokinetic analyses because of apparent noncompliance 
with armodafinil dosing. Systemic exposure following administration of 
armodafinil, as measured by steady-state AUC(τ) and C(max) values, was 
approximately 15% greater in elderly subjects compared with young subjects. 
Geometric mean ratios for AUC(τ) and C(max) in the two groups were 1.14 (95% CI 
1.03, 1.25; p = 0.0086) and 1.15 (95% CI 1.08, 1.24; p = 0.0002), respectively. 
When data were analysed for elderly subgroups, systemic exposure in the 
old-elderly group (age ≥75 years; n = 7) was 27% greater than in young subjects, 
as compared with 10% greater in the young-elderly group (age 65-74 years; 
n = 17). Although steady-state exposure to the metabolite R-modafinil acid was 
also higher in elderly than in young subjects (geometric mean ratios for AUC(τ) 
and C(max) were 1.73 and 1.61, respectively; p < 0.0001), there were no 
significant differences in systemic exposure to modafinil sulfone. Armodafinil 
was generally well tolerated by both groups. Headache (four subjects in each 
group), nausea (one in the elderly group and four in the young group), insomnia 
(two in the elderly group and one in the young group), and dizziness (two in the 
young group) were the most common adverse events.
CONCLUSIONS: Systemic exposure following administration of armodafinil is 
increased in the elderly in comparison with younger subjects, particularly in 
those aged ≥75 years. Although the increase in plasma armodafinil concentration 
in elderly subjects does not appear to result in more adverse events compared 
with young subjects, consideration should be given to the use of lower dosages 
of armodafinil for the management of excessive sleepiness in older patients, 
particularly the very elderly.