Editing Modafinil (section)

===Pharmacokinetics===
C<sub>max</sub> (peak levels) occurs approximately 2&nbsp;to&nbsp;3&nbsp;hours after modafinil administration.<ref name="pmid12537513"/> Food slows the absorption of modafinil but does not affect the total [[Area under the curve (pharmacokinetics)|area under the curve]] (AUC). ''In vitro'' measurements indicate that 60% of modafinil is bound to [[plasma protein]]s at clinical concentrations of the drug. This percentage changes very little when the concentration of modafinil is varied.<ref name="Hardman2001">{{cite book |vauthors=Gilman A, Goodman LS, Hardman JG, Limbird LE |title=Goodman & Gilman's the pharmacological basis of therapeutics |publisher=McGraw-Hill |location=New York |year=2001 |page=1984 |isbn=978-0-07-135469-1 }}</ref>

Renal excretion of unchanged modafinil usually accounts for less than 10% of an oral dose. This means that when modafinil is taken by mouth, the only approved route of administration, 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.<ref name="pmid12537513"/>

The two major circulating [[metabolite]]s 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.<ref name="pmid31951804"/><ref name="pmid26908128">{{cite journal | vauthors = Ramachandra B | title = A Critical Review of Properties of Modafinil and Analytical, Bioanalytical Methods for its Determination | journal = Critical Reviews in Analytical Chemistry | volume = 46 | issue = 6 | pages = 482–489 | date = November 2016 | pmid = 26908128 | doi = 10.1080/10408347.2016.1153948 | s2cid = 34069997 }}</ref> However, modafinil sulfone does appear to possess [[anticonvulsant]] effects, a property that it shares with modafinil.<ref name="pmid31951804"/><ref name="pmid15260124">{{cite journal | vauthors = Chatterjie N, Stables JP, Wang H, Alexander GJ | title = Anti-narcoleptic agent modafinil and its sulfone: a novel facile synthesis and potential anti-epileptic activity | journal = Neurochemical Research | volume = 29 | issue = 8 | pages = 1481–1486 | date = August 2004 | pmid = 15260124 | doi = 10.1023/b:nere.0000029559.20581.1a | s2cid = 956077 }}</ref>

[[Elimination half-life]] is in the range of 10 to 12 hours,<ref name="pmid12537513"/><ref name="Hardman2001"/> subject to differences in sex,<ref name="sleep-women-2016"/> in cytochrome P450 [[genotype]]s, liver function and renal function. Modafinil is metabolized mainly in the liver,<ref name="pmid12537513"/> 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.<ref name="Hardman2001"/>

Modafinil exhibits sex-specific pharmacokinetic differences.<ref name="sleep-women-2016" /> It demonstrates higher [[bioavailability]] in women compared to men. The mean C<sub>max</sub> is higher in women than in men, {{Val|5.2|u=mg/L}} vs. {{Val|4.2|u=mg/L}} (p < 0.05), following a single {{Val|200|u=mg}} oral dose of modafinil.<ref name="sleep-women-2016" /> This difference persists even after adjusting for body weight ({{Val|0.88|u=ml/min/kg}} vs. {{Val|0.72|u=ml/min/kg}}).<ref name="sleep-women-2016" /> 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.<ref name="sleep-women-2016" />