Modafinil in the Treatment of Debilitating Fatigue in Primary Biliary Cirrhosis A Clinical Experience

An assay was developed to determine concentrations of modafinil (dl-2-[(diphenylmethyl)sulfinyl]acetamide; Provigil) and its two major circulating metabolites, modafinil acid and modafinil sulfone, in human plasma. The assay utilized liquid-liquid extraction of the analytes and an internal standard, (phenylthio)acetic acid, from plasma into a mixture of hexane-dichloromethane-glacial acetic acid (55:45:2, v/v). The analytes were resolved isocratically on a narrow-bore phenyl column at a mobile phase flow-rate of 0.3 ml/min and were monitored by...

RATIONALE: Modafinil is a wakefulness-promoting drug which is likely to activate some wakefulness-promoting and/or inhibit sleep-promoting neurones in the brain. The locus coeruleus (LC) is a wakefulness-promoting noradrenergic nucleus whose activity can be "switched off" by the alpha2-adrenoceptor agonist clonidine, leading to sedative and sympatholytic effects. OBJECTIVE: The aim of the study is to compare the effects of single doses of modafinil and clonidine on arousal and autonomic functions in human volunteers. METHODS: Sixteen healthy ma...

Modafinil has been shown to promote wakefulness and some studies suggest the drug can improve cognitive function. Because of many similarities, the mechanism of action may be comparable to classical psychostimulants, although the exact mechanisms of modafinil's actions in wakefulness and cognitive enhancement are unknown. The current study aims to further examine the effects of modafinil as a cognitive enhancer on hippocampus-dependent memory in mice. A high dose of modafinil (75 mg/kg ip) given before training improved acquisition on a Morris ...

OBJECTIVE: This is one of two separate clinical trials to evaluate the efficacy and safety of modafinil, a novel wake-promoting agent, in patients with excessive daytime sleepiness (EDS) associated with narcolepsy. METHODS: In this 9-week, randomized, placebo-controlled, double-blind, 21-center clinical trial, patients were randomized to receive fixed daily doses of modafinil 200 mg, modafinil 400 mg, or placebo. A placebo-controlled, 2-week treatment discontinuation phase was included to evaluate the effects of withdrawal on patients who had b...

Coupled-column separation using restricted access media as the first dimension in order to exclude macromolecules and retain micromolecules has been successfully used for a number of biological fluids. This paper describes the first method developed and validated for the analysis in a single run of the enantiomers of modafinil and its two major metabolites. The method was developed using a bidimensional HPLC system by coupling a restricted access medium (RAM) bovine serum albumin (BSA) column (1.0 cm x 0.46 cm i.d.) to an amylose tris[(S)-1-phe...

Objective: We evaluated the effects of modafinil, a wake-promoting agent, on patient functioning, health-related quality of life, and nighttime and daytime sleep in patients with excessive sleepiness associated with shift work sleep disorder (SWSD).Method: A 12-week, randomized, double-blind, placebo-controlled study was performed at 31 centers in the United States between February 2001 and March 2002. Adults (N = 278) with excessive sleepiness associated with chronic SWSD (International Classification of Sleep Disorders criteria) were randomly...

(1) Modafinil, a psychostimulant, has been available in France for the treatment of narcolepsy and idiopathic hypersomnia since 1994. (2) The initial clinical file was inadequate to judge its possible clinical value. (3) In narcolepsy three new short-term clinical trials have compared modafinil with a placebo (nearly 500 patients treated with modafinil). (4) These trials show that the effects of modafinil on daytime drowsiness are only moderate (average reduction of one unwanted sleep episode a day) but are subjectively better than those of a p...