Wellbutrin (Bupropion) Elimination Timeline
Wellbutrin takes approximately 4-5 days to be substantially eliminated from your system, though complete clearance of all metabolites requires 7-9 days.
Elimination Half-Life and Clearance Timeline
The parent drug bupropion has a mean elimination half-life of 21 hours (±9 hours), meaning approximately half the drug is cleared from your body every 21 hours 1. Following the standard pharmacokinetic principle that a drug is essentially eliminated after 5 half-lives, bupropion itself is largely cleared within 4-5 days after the last dose 1, 2.
However, the complete picture is more complex due to active metabolites:
- Hydroxybupropion: elimination half-life of approximately 20 hours (±5 hours) 1
- Threohydrobupropion: elimination half-life of approximately 37 hours (±13 hours) 1, 3
- Erythrohydrobupropion: elimination half-life of approximately 33 hours (±10 hours) 1, 3
Complete System Clearance
The longest-lasting metabolite (threohydrobupropion) determines total elimination time. With a half-life of 37 hours, this metabolite requires approximately 7-9 days for complete clearance from the system (5 half-lives = 185 hours = 7.7 days) 1, 3.
Clinical Significance of Metabolites
These metabolites are not merely inactive byproducts—they contribute to bupropion's therapeutic effects 3, 4. At steady state, hydroxybupropion reaches plasma concentrations 4-7 times higher than the parent drug, with an AUC approximately 10-13 times greater than bupropion itself 1, 3. This means the metabolites remain pharmacologically active in your system well after the parent drug has cleared 3, 4.
Important Clinical Considerations
For drug interaction purposes, allow at least 7-9 days after stopping bupropion before starting medications that interact with it, particularly MAOIs (which require a 14-day washout period for safety) 5. The extended presence of active metabolites means therapeutic effects—and potential side effects—may persist for several days after discontinuation 3.
For therapeutic drug monitoring, steady-state conditions are reached within 8 days of consistent dosing, and the same timeframe applies in reverse for complete elimination 1.