What is the half-life of bupropion (Wellbutrin)

Half-Life of Bupropion

The mean elimination half-life of bupropion is 21 (±9) hours according to FDA drug labeling, with its active metabolites having longer half-lives ranging from 20-37 hours. 1

Pharmacokinetic Profile of Bupropion

Bupropion undergoes extensive metabolism in the body, resulting in three active metabolites with significant clinical implications:

• Parent compound (bupropion):

  • Mean elimination half-life: 21 ± 9 hours 1
  • Reaches steady-state plasma concentration within 8 days of chronic dosing 1

• Active metabolites:

  1. Hydroxybupropion:

     • Half-life: approximately 20 ± 5 hours 1
     • At steady state, reaches plasma concentrations about 7 times higher than the parent drug
     • Has about 50% of the potency of bupropion

  2. Threohydrobupropion:

     • Half-life: approximately 37 ± 13 hours 1
     • Longer-acting metabolite

  3. Erythrohydrobupropion:

     • Half-life: approximately 33 ± 10 hours 1
     • Also contributes to the overall clinical effect

Formulation Differences

The half-life remains consistent across formulations, but absorption profiles differ:

• Immediate-release (IR): Peak plasma concentration at approximately 1.5 hours 2
• Sustained-release (SR): Peak plasma concentration at approximately 3 hours 2
• Extended-release (XL): Peak plasma concentration at approximately 5 hours 1, 2

Clinical Implications

The relatively long half-life of bupropion and its active metabolites has important clinical implications:

• Dosing frequency: The extended half-life supports once-daily dosing with XL formulation, twice-daily with SR formulation, and three-times daily with IR formulation 2

• Drug interactions: Bupropion inhibits CYP2D6 and may reduce clearance of medications metabolized by this enzyme 1

• Steady state: When initiating therapy, it takes approximately 8 days to reach steady-state plasma concentrations 1

• Withdrawal considerations: The long half-life of metabolites means that effects may persist for days after discontinuation

Special Populations

• Renal impairment: In patients with moderate to severe renal impairment, dosage should be reduced by half 3

• Hepatic impairment: In patients with moderate to severe hepatic impairment, dosage should be limited to once daily 3

• Breastfeeding considerations: Bupropion and its metabolites are present in breast milk, with the long half-life potentially contributing to accumulation in infants 4

The long half-life of bupropion and its active metabolites contributes to its efficacy in various indications including depression, smoking cessation, and weight management when combined with naltrexone.