C (peak levels) occurs approximately 2 to 3 hours after modafinil administration. Food slows absorption of modafanil, but does not affect the total AUC. In vitro measurements indicate that 60% of modafinil is bound to plasma proteins at clinical concentrations of the drug. This percentage changes very little when the concentration of modafinil is varied.
Renal excretion of unchanged modafinil usually accounts for less than 10% of an oral dose. This means that when modafinil is taken by mouth, less than 10% of the drug is eliminated from the body through the urine without being metabolized by the liver or other organs. The rest of the drug is either metabolized or excreted through other routes, such as feces or bile.
The two major circulating metabolites of modafinil are modafinil acid (CRL-40467) and modafinil sulfone (CRL-41056). Both of these metabolites have been described as inactive, and neither appears to contribute to the wakefulness-promoting effects of modafinil. However, modafinil sulfone does appear to possess anticonvulsant effects, a property that it shares with modafinil.
Elimination half-life is in the range of 10 to 12 hours, subject to differences in sex, in cytochrome P450 genotypes, liver function and renal function. Modafinil is metabolized mainly in the liver, and its inactive metabolites are excreted in the urine. Urinary excretion of the unchanged drug is usually less than 10%, but can range from 0% to as high as 18.7%, depending on the factors mentioned.
Modafinil exhibits sex-specific pharmacokinetic differences. It demonstrates higher bioavailability in women compared to men. The mean C is higher in women than in men,  vs.  (p < 0.05), following a single  oral dose of modafinil. This difference persists even after adjusting for body weight ( vs. ). The clearance of modafinil is 30% higher in men than in women, and plasma concentrations after a single dose are significantly higher in women than in men. These sex-specific pharmacokinetic differences may have implications for the efficacy and safety of modafinil.