Half-Life of Modafinil
The half-life of modafinil is approximately 15 hours after multiple doses, with steady state reached after 2-4 days of dosing. 1, 2, 3
Pharmacokinetic Details
The effective elimination half-life is about 15 hours following multiple-dose administration, which is the clinically relevant parameter for therapeutic use 3
After single-dose administration, the elimination half-life ranges from 12-15 hours, though this varies slightly depending on the study methodology 4
The racemic mixture contains two enantiomers with markedly different half-lives:
Clinical Implications
At steady state, R-modafinil comprises 90% of circulating drug and S-modafinil only 10%, due to the differential elimination rates 3
Steady state concentrations are achieved after 2-4 days of once-daily dosing, making this the timeframe for full therapeutic effect 1, 2, 3
The relatively long half-life allows for once-daily dosing in the morning, though some patients may benefit from split dosing (morning and midday) 1
Important Caveats
In elderly patients and those with hepatic or renal impairment, the elimination half-life may be prolonged, requiring dose adjustments 3, 4
Auto-induction of metabolizing enzymes (particularly CYP3A4) can occur with chronic use, potentially decreasing trough levels after multiple weeks, though the clinical significance appears minimal 3