A double-blind,
placebo-controlled, ascending-dose evaluation of the pharmacokinetics and
tolerability of modafinil tablets in healthy male volunteers
Wong YN, Simcoe D, Hartman LN, Laughton WB,
King SP, McCormick GC, Grebow PE
Drug Safety and Disposition,
Cephalon, Inc.
West Chester, Pennsylvania, USA.
J Clin Pharmacol 1999 Jan; 39(1):30-40
ABSTRACT
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.
1. modafinil is
a potential treatment for
fibromyalgia
2. modafinil improves
fatigue in patients with multiple sclerosis
3. modafinil offers
promise as an augmentation to antidepressants
4. modafinil excessive sleepiness in
Parkinson's disease
5. modafinil excessive
daytime sleepiness in Parkinson's disease
6. modafinil may
be useful for attention-deficit/hyperactivity disorder
7. modafinil benefits
cerebral palsy in an unknown way
8. modafinil
article
9. modafinil
amplification of cortical serotonin release
10. modafinil
treatment of alcoholic organic brain syndrome
11. modafinil
effect on melatonin, cortisol, and growth hormone
12. modafinil
in obstructive sleep apnea-hypopnea syndrome
13. modafinil
vs dextroamphetamine in treatment of adult ADHD
14. modafinil
efficacy in narcolepsy
15. modafinil
switching from narcolepsy drugs to modafinil
16. modafinil
drug of choice for narcolepsy
17. modafinil
dopaminergic transmission mediates CNS stimulants
18. modafinil
for daytime sleepiness in sleep apnea
19. modafinil
treatment of residual excessive daytime sleepiness
20. modafinil
in the treatment of
narcolepsy
21. modafinil
and naps as counter measures in sleep deprivation
22. modafinil
effect on narcolepsy
23. modafinil
as a treatment for excessive daytime sleepiness
24. modafinil
a narcolepsy study
25. modafinil
use in a sleep deprivation experiment
26. modafinil for
sustaining the alertness of helicopter pilots
27. modafinil the
unique properties of a new stimulant
28. modafinil dosage
and safety
29. modafinil in treatment of fatigue in
multiple sclerosis
30. modafinil non-addictive potential of modafinil
31. modafinil successful
treatment of hypersomnia & narcolepsy
32. modafinil physiological effects of modafinil in drug abusers
33. modafinil narcolepsy:
symptoms and management
34. modafinil cognitive enhancing effects of modafinil
