What is the elimination half-life of bupropion (Wellbutrin) from the body?

Bupropion Elimination Half-Life and Time to Clear from the Body

Bupropion has a mean elimination half-life of approximately 21 hours (±9 hours) after chronic dosing, meaning it takes roughly 4-5 days (about 5 half-lives) for the parent drug to be essentially eliminated from the body. 1

Parent Drug Elimination

• The elimination half-life of bupropion itself is 21 hours (±9 hours) after chronic dosing 1
• Steady-state plasma concentrations are reached within 8 days of regular dosing 1
• Following oral administration, 87% of the radioactive dose is recovered in urine and 10% in feces, with only 0.5% excreted as unchanged bupropion 1
• This indicates extensive hepatic metabolism before elimination 1

Active Metabolites Take Much Longer to Clear

The active metabolites of bupropion have significantly longer elimination half-lives than the parent drug, which is clinically important because their plasma concentrations are as high as or higher than bupropion itself. 1

Hydroxybupropion (Primary Active Metabolite)

• Elimination half-life: approximately 20 hours (±5 hours) 1
• At steady state, the AUC is approximately 17 times that of bupropion 1
• Peak concentration occurs approximately 6 hours post-dose and is about 10 times the peak level of the parent drug at steady state 1

Threohydrobupropion and Erythrohydrobupropion

• Elimination half-lives: 37 hours (±13 hours) and 33 hours (±10 hours), respectively 1
• These are significantly longer than the parent drug 1
• Steady-state AUCs are 7 times and 1.5 times that of bupropion, respectively 1

Clinical Implications for Complete Drug Clearance

Given the longest metabolite half-life of approximately 37 hours for threohydrobupropion, complete elimination of bupropion and all active metabolites takes approximately 7-9 days (5 half-lives of the longest-lived metabolite). 1

Special Populations with Delayed Clearance

Patients with renal or hepatic impairment experience significantly prolonged elimination and accumulation of bupropion and its metabolites. 1

Renal Impairment

• In moderate-to-severe renal impairment (GFR 30.9 ± 10.8 mL/min), exposure to bupropion is approximately 2-fold higher after a single dose 1
• Hydroxybupropion and threohydrobupropion metabolites show 2.3-fold and 2.8-fold increases in AUC, respectively, in end-stage renal failure 1
• Dose reduction by half is recommended for patients with moderate to severe renal impairment 2, 3

Hepatic Impairment

• In alcoholic liver disease, the half-life of hydroxybupropion is significantly longer (32 ± 14 hours vs 21 ± 5 hours in healthy volunteers) 1
• In severe hepatic cirrhosis, bupropion AUC increases 3.12-fold and half-life increases 1.43-fold 1
• Hydroxybupropion shows a 3.88-fold increase in half-life in severe cirrhosis 1
• Maximum daily dose should not exceed 150 mg in moderate to severe hepatic impairment 2, 3

Practical Timeline for Drug Washout

• Parent drug (bupropion): Essentially cleared in 4-5 days (5 × 21 hours = 105 hours) 1
• All active metabolites: Essentially cleared in 7-9 days (5 × 37 hours = 185 hours for threohydrobupropion) 1
• In renal or hepatic impairment: Clearance may take 2-3 times longer (14-21 days or more) 1

Important Caveats

The extensive metabolism and long-lived active metabolites mean that clinical effects and drug interactions may persist for over a week after discontinuation, particularly in patients with renal or hepatic dysfunction. 1

• Bupropion inhibits CYP2D6, so drug interactions with medications metabolized by this enzyme may persist for 7-9 days after stopping 1, 4
• The seizure risk associated with bupropion may theoretically persist until metabolites are cleared 2, 1
• For procedures requiring opioid analgesia in patients taking naltrexone-bupropion combinations, the medication should be discontinued well in advance to allow complete clearance 2