Open-label, single-dose pharmacokinetic study of modafinil tablets: Influence of age and gender in normal subjects

An open-label, single-center, single-dose, parallel-group study was perform ed in healthy young males and females as well as healthy elderly males to e xamine the influence of age and gender on the pharmacokinetics of modafinil following administration of a single 200 mg oral dose. Twelve subjects wer e enrolled in each of the following three groups: young males, young female s, and elderly males. Each fasted (over night) subject received 2 x 100 mg modafinil tablets. Blood and urine samples were collected at various times up to 72 hours postdose for the determination of plasma and urine levels of modafinil as well as the acid and sulfone metabolites. The plasma concentr ations of the individual isomers, d- and l-modafinil, were also determined. Pharmacokinetic parameters were determined by noncompartmental methods. Mo dafinil was well tolerated at a single oral dose of 200 mg The most commonl y reported adverse events were headache, fever, pharyngitis, and asthenia. There were no clinically meaningful differences with respect to the inciden ce rate of treatment emergent adverse events among the young female, young male, and old male groups. Modafinil was rapidly absorbed after oral dosing and slowly cleared (t(1/2) similar to 11-14 hr) from the body. Modafinil a cid was the major urinary metabolite, which accounted for 35% to 60% of the dose. Results from this study indicated that there were age and gender eff ects on modafinil clearance processes. In this regard, the clearance rate o f modafinil in males decreased with age while young females cleared modafin il at a faster rate than young males. Stereospecific pharmacokinetics of mo dafinil were also demonstrated. The d-modafinil was eliminated three times faster than the d-modafinil. Journal of Clinical Pharmacology, 1999;39:282- 288 (C) 1999 the American College of Clinical Pharmacology.