A randomized, double-blind, placebo-controlled, ascending-dose study was conducted to evaluate the pharmacokinetic and safety profiles of increasing modafinil doses (200 mg, 400 mg, 600 mg, 800 mg) administered orally over a 7-day period in normal healthy male volunteers. Eight subjects (six modafinil; two placebo) were randomized to each of the four dose groups. Modafinil or a placebo was administered once daily for 7 days. Serial blood samples were obtained following administration of the day 1 and day 7 doses for characterization of pharmacokinetics, and trough samples were obtained prior to dosing on days 2 through 6 to assess the time to reach the steady state. Pharmacokinetic parameters were calculated using noncompartmental methods. Modafinil steady state was reached after three daily doses. Modafinil pharmacokinetics were dose and time independent over the range of 200 mg to 800 mg. Steady-state pharmacokinetics of modafinil were characterized by a rapid oral absorption rate, a low plasma clearance of approximately 50 mL/min, a volume of distribution of approximately 0.8 L/kg, and a long half-life of approximately 15 hr. Modafinil was primarily eliminated by metabolism. Modafinil acid was the major urinary metabolite. Stereospecific pharmacokinetics of modafinil were demonstrated. The d-modafinil enantiomer was eliminated at a threefold faster rate than 1-modafinil. Modafinil 200 mg, 400 mg, and 600 mg doses were generally well tolerated. The modafinil 800 mg dose panel was discontinued after 3 days of treatment due to the observation of increased blood pressure and pulse rate. The safety data from this study suggest that the maximum tolerable single daily oral modafinil dose, without titration, may be 600 mg.

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Modafinil research

 1.   Modafinil  for sustaining the alertness of helicopter pilots
 2.   Modafinil  augmentation of antidepressant treatment
 3.   Modafinil  the unique properties of a new stimulant 
 4.   Modafinil  children with attention-deficit/hyperactivity disorder
 5.   Modafinil  tolerability in healthy male volunteers
 6.   Modafinil  successful treatment of hypersomnia & narcolepsy
 7.   Modafinil  narcolepsy: symptoms and management
 8.   Modafinil  amplification of cortical serotonin release
 9.   Modafinil  treatment of alcoholic organic brain syndrome
10.  Modafinil  effect on melatonin, cortisol, and growth hormone
11.  Modafinil  in obstructive sleep apnea-hypopnea syndrome

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