 |
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.
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
|
|
|
|
|
