Pharmacokinetics and Safety of Armodafinil in Chinese Healthy Humans After Multiple-Dose Oral Administration

Abstract

Armodafinil, the R-enantiomer of modafinil that promotes wakefulness, was studied regarding its pharmacokinetics and safety in healthy Chinese subjects after multiple-dose oral administration (200 mg daily for 7 days). Twelve subjects participated in this single-center, self-contrast study. The plasma concentrations of armodafinil and its metabolites (R-modafinil acid and modafinil sulfone) were measured by ultra-performance liquid chromatography–tandem mass spectrometry, and drug safety was evaluated during the study. The steady-state accumulation ratio of armodafinil was 1.5, and its metabolites also accumulated with ratios of 1.3 and 7.8, respectively. Although the mean steady-state half-life was similar to that after a single dose, the area under the concentration–time curve, maximum plasma concentration, and clearance of armodafinil changed significantly after multiple dosing. The drug was safe with no serious adverse events, yet fever occurred in 6 subjects, which was not reported before. Modafinil sulfone had significant accumulation, implying the need for further study on its central nervous system–activating properties in Chinese patients.