PURPOSE: Residual excessive sleepiness (ES) persists in approximately 52% of patients with obstructive sleep apnea (OSA) even after regular continuous positive airway pressure (CPAP) usage of ≥ 6 hours a night. Armodafinil, the R-enantiomer of modafinil, is a next generation, non-amphetamine, wakefulness-promoting agent known to improve residual ES in patients with OSA who are regular users of CPAP. Compared with modafinil, the pharmacokinetic profile of armodafinil produces a higher sustained plasma concentration throughout the day in healthy subjects, suggesting that armodafinil may provide sustained therapeutic benefit later in the day in patients with residual ES associated with OSA despite regular CPAP use.
METHODS: Using plasma concentration data obtained following 7 days of once-daily administration, post hoc analyses were conducted on pharmacokinetic data from healthy subjects administered armodafinil (n=34) or modafinil (n=18). Comparisons were made on a milligram-to-milligram basis between the two agents. Average plasma concentration was calculated across time points later in the day. Concentration swing and fluctuation were measured during a dosing interval using concentration ratios (Cmax-Cmin)/Cmin and (Cmax-Cmin)/Cavg, respectively.
RESULTS: Average plasma concentration late in the day was approximately 50% higher for armodafinil compared with modafinil. Swing and fluctuation magnitude for armodafinil were 42% and 28% lower, respectively, than for modafinil.
CONCLUSION: After multiple dosing, armodafinil produces a higher average concentration later in the day and less swing and fluctuation in concentrations across the dosing interval compared with modafinil after multiple doses.
CLINICAL IMPLICATIONS: Armodafinil pharmacokinetic characteristics may provide a sustained and more stable therapeutic benefit throughout the day in patients with residual ES associated with OSA despite regular CPAP use.
DISCLOSURE: Mona Darwish, Shareholder Mona Darwish, Edward T. Hellriegel and Philmore Robertson, JR receive stock or stock options from Cephalon, Inc.; Employee Mona Darwish, Edward T. Hellriegel, Mary Kirby, and Philmore Robertson JR. are all Cephalon, Inc. employees.; No Product/Research Disclosure Information