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Single‐Dose Pharmacokinetics of Modafinil and Methylphenidate Given Alone or in Combination in Healthy Male Volunteers
Author(s) -
Wong Y. Nancy,
King S. Peter,
Laughton Watson B.,
McCormick George C.,
Grebow Peter E.
Publication year - 1998
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1998.tb04425.x
Subject(s) - modafinil , methylphenidate , pharmacokinetics , pharmacology , volume of distribution , pharmacodynamics , chemistry , medicine , attention deficit hyperactivity disorder , psychiatry
Modafinil is a novel wake‐promoting agent being developed for treatment of excessive daytime sleepiness associated with narcolepsy. An open, 3 × 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 (t 1/2 ), maximum concentration (C max ), area under the concentration—time curve (AUC 0–∞ ), total clearance (Cl/F), and apparent volume of distribution (Vd/F) for modafinil and t 1/2 , C max , and AUC 0–∞ for modafinil acid were not affected by concomitant administration of methylphenidate. Small but statistically significant increases in time to C max (t max ) 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.