PHARMACOKINETIC PROFILE OF MODAFINIL

The pharmacokinetics of modafinil have been studied in mouse, rat, rab bit, dog and humans in a large range of doses. In humans modafinil exh ibits linear kinetics, with plasma concentrations and AUC increasing p roportionally with dose after either single or repeated administration . The t(1/2) ranges from 10-15 h and allows a once- or twice-daily adm inistration. The extent of plasma protein binding is approximately 60% . Modafinil is extensively metabolized. The percentage of unchanged mo dafinil excreted in the urine is low (< 10% of the administered dose). The main metabolite, modafinil acid, is inactive and excreted unconju gated in the urine (40-60% of the administered dose). The pharmacokine tics of modafinil are not modified by food but are altered in patients with severe hepatic and renal disease. Therefore, a 50% dose reductio n is recommended in patients with hepatic insufficiency or chronic ren al failure.