Pharmacokinetics and tolerability of modafinil tablets in Chinese subjects

Summary Objective: To investigate the pharmacokinetics and tolerability of modafinil in Chinese subjects. Methods: Twelve healthy volunteers were given an escalating single dose of modafinil (100, 200 and 400 mg) in a three‐period study (study 1). Another 12 volunteers received 100 mg twice daily for 7 days in multiple‐dose study (study 2). Blood samples were taken from 0 to 60 h for study 1. And samples for study 2 were collected before administration on three consecutive morning and then from 0 to 60 h after the last dose. Pharmacokinetic parameters were calculated and compared with results from published data. Results: In study 1, Cmax and area under the concentration–time curve of modafinil and modafinil acid were increased proportionally with dose levels; t1/2 was independent on the dose levels. In study 2, the steady state was reached on day 4, and mean trough plasma concentration of modafinil was 1·36 ± 0·34 μg/mL. Apparent plasma clearance and apparent volume of distribution were lower in 100 mg twice‐daily group than those in 100 mg single group. The adverse events were mild and moderate in study 1 and 2. Conclusions: In this pharmacokinetic study, modafinil was safe and well tolerated by young healthy Chinese subjects. The major pharmacokinetic parameters of modafinil in Chinese subjects are similar to those reported in Caucasians although the half‐life seems to be longer in the former than in the latter. This apparent difference requires investigation.