How long does modafinil (provigil) stay in your system?

How Long Does Modafinil Stay in Your System?

Modafinil has an elimination half-life of approximately 12-15 hours, with complete clearance typically occurring within 2-4 days after the last dose. 1, 2

Pharmacokinetic Profile

• Absorption: Modafinil is readily absorbed after oral administration

  • Peak plasma concentrations occur at 2-4 hours after administration 1
  • Food does not affect overall bioavailability but may delay peak concentration by approximately 1 hour 1

• Distribution:

  • Apparent volume of distribution is approximately 0.9 L/kg
  • Moderately bound to plasma proteins (approximately 60%), mainly to albumin 1

• Metabolism and Elimination:

  • Primary route is metabolism (approximately 90%), mainly in the liver
  • Less than 10% of the dose is excreted as unchanged drug
  • Metabolism occurs through hydrolytic deamidation, S-oxidation, aromatic ring hydroxylation, and glucuronide conjugation 1, 2
  • Subsequent renal elimination of metabolites (80% in urine vs. 1% in feces) 1

Important Pharmacokinetic Considerations

Enantiomer Differences

• Modafinil is a 1:1 racemic compound with different pharmacokinetics for each enantiomer
• R-modafinil has approximately three times the half-life of S-modafinil 1
• At steady state, total exposure to R-modafinil is approximately three times that of S-modafinil 1, 3

Steady State

• Steady state is reached within 2-4 days of daily dosing 1, 2
• The effective elimination half-life after multiple doses is about 15 hours 1

Special Populations

• Elderly: A slight decrease (approximately 20%) in oral clearance observed in older adults
• Geriatric patients: In patients with mean age of 82 years, plasma levels were approximately two times those of younger subjects 1
• Hepatic/Renal Impairment: Elimination processes can be slowed, potentially extending the time modafinil remains in the system 2

Detection Window

Based on the pharmacokinetic profile, modafinil can typically be detected in:

• Blood/plasma: Up to 2-3 days after last dose
• Urine: Up to 4-5 days after last dose (primarily as metabolites)

Clinical Implications

• The long half-life allows for once-daily dosing, typically in the morning 4
• Unlike some other stimulants, modafinil does not appear to have withdrawal phenomena after treatment cessation 5
• Modafinil may interact with medications metabolized by certain CYP enzymes, particularly CYP3A4 substrates like hormonal contraceptives 2

Comparison to Armodafinil

Armodafinil (R-modafinil) has a similar terminal half-life to modafinil (approximately 13 hours) but maintains higher plasma concentrations later in the day due to its different pharmacokinetic profile 3:

• Armodafinil plasma concentrations decline in a monophasic manner
• Modafinil concentrations decline in a biphasic manner due to rapid elimination of the S-isomer 3

This pharmacokinetic understanding is important for patients taking modafinil, as it helps explain the duration of therapeutic effects and potential for drug interactions during the period it remains in the system.