How long does bupropion remain in the body of a healthy adult taking a therapeutic extended‑release dose?

How Long Bupropion Stays in Your System

Bupropion has an elimination half-life of approximately 21 hours, meaning it takes roughly 4–5 days (about 5 half-lives) for the drug to be essentially cleared from your body after stopping. However, its active metabolites persist significantly longer—hydroxybupropion has a half-life of approximately 20 hours, while threohydrobupropion and erythrohydrobupropion have half-lives of approximately 37 and 33 hours, respectively, requiring 7–9 days for complete elimination. 1, 2

Parent Drug Elimination

• Bupropion itself reaches steady-state plasma concentrations within 8 days of chronic dosing and has a mean elimination half-life of 21 hours (±9 hours). 1
• After a single 100 mg oral dose in healthy volunteers, the elimination half-life ranged from 8 to 16.5 hours, with some variability between individuals. 3, 4, 5
• Following the standard "5 half-lives to clearance" pharmacokinetic principle, bupropion is eliminated from plasma in approximately 4–5 days after the last dose. 1, 2

Active Metabolite Persistence

• Hydroxybupropion, the primary active metabolite formed via CYP2B6, has an elimination half-life of approximately 20 hours (±5 hours), requiring roughly 4–5 days for clearance. 1, 2
• Threohydrobupropion and erythrohydrobupropion have significantly longer half-lives of approximately 37 hours (±13 hours) and 33 hours (±10 hours), respectively, meaning these metabolites persist for 7–9 days after discontinuation. 1, 2, 5
• At steady state, hydroxybupropion concentrations are 4- to 7-fold higher than bupropion at peak, with an AUC approximately 10- to 13-fold greater than the parent drug. 1, 2
• Threohydrobupropion reaches steady-state AUC levels 7 times that of bupropion, while erythrohydrobupropion reaches 1.4 times that of bupropion. 1

Clinical Implications of Metabolite Activity

• Hydroxybupropion retains approximately 50% of bupropion's pharmacologic activity, while threohydrobupropion and erythrohydrobupropion retain approximately 20% activity based on animal models. 2
• Because metabolite plasma concentrations are as high or higher than bupropion itself, the clinical effects of bupropion may persist for up to 7–9 days after the last dose due to lingering active metabolites. 1, 2

Special Population Considerations

Hepatic Impairment

• In patients with alcoholic liver disease, the elimination half-life of the morpholinol metabolite (hydroxybupropion) is significantly prolonged to 32.2 hours (±13.5 hours) compared to 21.1 hours (±4.9 hours) in healthy subjects, extending clearance time to 6–7 days for this metabolite. 4
• Mean AUC values for bupropion and all metabolites are increased in hepatic impairment, though high inter-individual variability makes precise predictions difficult. 4

Pediatric Patients

• In youths aged 11–17 years, bupropion has a significantly shorter mean half-life of 12.1 hours compared to adults (21 hours), suggesting faster clearance in approximately 2.5–3 days. 6
• However, threohydrobupropion half-life in youths is 26.3 hours, still shorter than the 37 hours observed in adults, but metabolite-to-parent AUC ratios are 19–80% higher in youths, indicating relatively greater metabolite accumulation. 6

Practical Timeline Summary

For a healthy adult on therapeutic extended-release dosing:

• Bupropion parent drug: Essentially cleared in 4–5 days 1, 2
• Hydroxybupropion: Cleared in 4–5 days 1, 2
• Threohydrobupropion and erythrohydrobupropion: Cleared in 7–9 days 1, 2, 5
• Complete system clearance (all active compounds): Approximately 7–9 days after the last dose 1, 2, 5

Important Caveats

• Only 0.5% of an oral bupropion dose is excreted unchanged in urine; 87% is recovered as metabolites in urine and 10% in feces, meaning renal and hepatic function significantly impact clearance. 1
• Factors altering metabolic capacity—including liver disease, congestive heart failure, age, and concomitant medications—will prolong elimination times for both bupropion and its metabolites. 1
• Drug interaction considerations persist for approximately 7–9 days after stopping bupropion, particularly for medications metabolized by CYP2D6 (which bupropion inhibits) or CYP2B6 (which metabolizes bupropion). 1, 2