How long does it take for bupropion (Wellbutrin) to be completely eliminated from the system?

Bupropion (Wellbutrin) Elimination Timeline

Bupropion is essentially eliminated from your system within 4-5 days after the last dose, though complete clearance of all metabolites takes approximately 7-10 days. 1

Parent Drug Elimination

• Bupropion itself has an elimination half-life of approximately 21 hours (±9 hours), meaning the parent drug concentration is reduced by half every 21 hours 1, 2
• After 5 half-lives (approximately 4-5 days), over 97% of bupropion is eliminated from the bloodstream 1
• Peak plasma concentrations occur around 5 hours after taking the extended-release formulation 1

Active Metabolite Clearance

The complete elimination timeline is actually determined by bupropion's active metabolites, which persist longer than the parent drug:

• Hydroxybupropion (the primary active metabolite) has a half-life of approximately 20 hours (±5 hours), similar to bupropion itself 1, 2
• Threohydrobupropion has a significantly longer half-life of approximately 37 hours (±13 hours) 1, 2
• Erythrohydrobupropion has a half-life of approximately 33 hours (±10 hours) 1, 2

Complete System Clearance

• The longest-lasting metabolite (threohydrobupropion) requires approximately 7-10 days for complete elimination (5 half-lives × 37 hours = ~8 days) 1, 2
• At steady state, these metabolites accumulate to concentrations significantly higher than the parent drug, with hydroxybupropion reaching AUC levels approximately 13 times that of bupropion 1

Clinical Implications

For drug interaction purposes, allow at least 7-10 days after stopping bupropion before starting medications that may interact, particularly MAOIs, which require a 14-day washout period 3

• Bupropion inhibits CYP2D6 enzyme activity, so this inhibitory effect persists until the drug and metabolites are cleared 2
• The extended half-lives of active metabolites mean therapeutic effects (and potential side effects) may persist for several days after discontinuation 2

Factors Affecting Elimination

Hepatic impairment significantly prolongs elimination since bupropion undergoes extensive hepatic metabolism via CYP2B6 1, 2

• Patients with moderate to severe hepatic impairment may experience substantially delayed clearance 3
• Renal impairment also affects clearance, as metabolites are renally excreted, requiring dose reduction by half in patients with GFR <90 mL/min 3