A Double-Blind, Placebo-Controlled, Ascending-Dose Evaluation of the Pharmacokinetics and Tolerability of Modafinil Tablets in Healthy Male Volunteers

Share on facebook
Share on linkedin
Share on twitter
Share on email
antidepressant

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.

This post is a Research-Based topic

Modafinil.com follows the strictest sourcing guidelines in the health and nootropics industry. Our focus is to exclusively link to peer-reviewed studies found on respected websites, like PubMed. We focus on finding the most accurate information from the scientific source.

Our goal is to provide you with the most scientifically accurate, unbiased, and comprehensive information regarding Modafinil and Armodafinil.

All of our content is written by people with a strong science background, including medical researchers.

Our content is continually monitored by an internal peer-review process to ensure accuracy. We strive to never have a piece of inaccurate information on this website.

If you feel that any of our content is inaccurate or out-of-date, please contact us at: [email protected]