Single‐Dose Pharmacokinetics of Modafinil and Methylphenidate Given Alone or in Combination in Healthy Male Volunteers

Abstract

Modafinil is a novel wake-promoting agent being developed for treatment of excessive daytime sleepiness associated with narcolepsy. An open, 3 x 3 Latin square, randomized, cross-over study was performed in healthy males to compare the pharmacokinetics of single-dose oral modafinil (200 mg) and methylphenidate (40 mg) administered alone or in combination. Blood samples were obtained for analysis of d- and l-threo-methylphenidate and modafinil and its acid and sulfone metabolites. Pharmacokinetic parameters were determined by noncompartmental methods, but could not be evaluated for modafinil sulfone due to plasma levels that were close to the assay quantitation limit. Although sporadic differences in plasma concentrations were observed between treatments, coadministration of modafinil and methylphenidate did not significantly alter the plasma concentrations of modafinil, modafinil acid, modafinil sulfone, or methylphenidate enantiomers compared with administration of these agents alone. Half-life (t1/2), maximum concentration (Cmax), area under the concentration-time curve (AUC0-infinity), total clearance (Cl/F), and apparent volume of distribution (Vd/F) for modafinil and t1/2, Cmax, and AUC0-infinity for modafinil acid were not affected by concomitant administration of methylphenidate. Small but statistically significant increases in time to Cmax (tmax) were observed for modafinil and modafinil acid after methylphenidate coadministration compared with modafinil alone. Modafinil coadministration did not significantly alter the pharmacokinetics of d- or l-threo-methylphenidate, except for a small decrease in Vd/F of l-threo-methylphenidate. Concomitant methylphenidate may cause a delay in the oral absorption of modafinil, but this delay might not be relevant clinically. Coadministration did not alter the extent of oral absorption and disposition of either agent. Therefore, a pharmacokinetic interaction between modafinil and methylphenidate would be unlikely.

Pharmacokinetic Study of Modafinil in Relation to Gender and Ethnicity in Healthy Young Chinese Volunteers

“…The results of pharmacokinetic parameters are consistent with those reported by others (24)(25)(26) and could be served as the basic of the evaluation for the influence of ethnicity and sex.…”

Modulation of the Acoustic Startle Response by the Level of Arousal: Comparison of Clonidine and Modafinil in Healthy Volunteers

“…The doses were chosen on the basis of the current literature (modafinil: Taneja et al, 2005;clonidine: Morley et al, 1991;Bitsios et al, 1996;Phillips et al, 2000c, d). The time required to attain peak plasma concentrations (t MAX ) of clonidine and modafinil after the ingestion of single doses is approximately 2 h (modafinil: Wong et al, 1998;clonidine: Lowenthal et al, 1988), and the time course of the sessions was designed to ensure peak plasma concentrations of the drugs at the start of the post-treatment testing.…”

Modafinil Improves Cognition and Attentional Set Shifting in Patients with Chronic Schizophrenia

“…Peak plasma concentrations of modafinil are obtained 2-3 h after oral administration with an elimination half-life of 10-12 h (Wong et al, 1998). Patients were, therefore, tested 2 h post drug administration, for approximately 2 h.…”