Steady-state pharmacokinetics and tolerability of modafinil given alone orin combination with methylphenidate in healthy volunteers

The potential for a pharmacokinetic (PK) drug-drug interaction between modo finil and methylphenidate, each at steady state, was investigated in an ope n-label, randomized, single-period study in 32 healthy male and female volu nteers, All subjects received modafinil once daily orally for 28 days (200 mg on Days 1-7 and 400 mg on Days 8-28). On Days 22 to 28, half of the subj ects also received 20 mg of methylphenidate orally 8 hours after their moda finil dose. FK profiles of modofinil were obtained on Days 21 and 28 and co mpared between the two groups. There were no statistically significant diff erences between the treatment groups in the mean changes in PK parameters f or modafinil, Parameters for its metabolites were also similar between the groups, and all treatments were well tolerated. The results indicate that a dministration of low-dose methylphenidate 8 hours after treatment with moda finil does not appear to alter the steady-state pharmacokinetics of modafin il in healthy volunteers. (C) 2001 the American College of Clinical Pharmac ology.