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

Half-Life of Bupropion (Wellbutrin)

The mean elimination half-life of bupropion is 21 (±9) hours, as indicated in the FDA drug label. 1

Pharmacokinetic Profile of Bupropion

Bupropion undergoes extensive metabolism in the body, resulting in three active metabolites with their own half-lives:

• Parent drug (bupropion): 21 (±9) hours 1
• Hydroxybupropion (primary active metabolite): approximately 20 (±5) hours 1
• Threohydrobupropion: approximately 37 (±13) hours 1
• Erythrohydrobupropion: approximately 33 (±10) hours 1

Metabolite Activity and Concentrations

The metabolites of bupropion contribute significantly to its clinical effects:

• Hydroxybupropion is approximately 50% as potent as bupropion, but its plasma concentration at steady state is about 7 times higher than the parent drug 1
• Threohydrobupropion and erythrohydrobupropion are about 5-fold less potent than bupropion 1
• At steady state, the AUC (area under the curve) of hydroxybupropion is approximately 13 times that of bupropion 1

Formulation Differences

The pharmacokinetic profile varies slightly between different formulations of bupropion:

• Immediate Release (IR): Peak plasma concentration reached in approximately 1.5 hours 2
• Sustained Release (SR): Peak plasma concentration reached in approximately 3 hours 2
• Extended Release (XL): Peak plasma concentration reached in approximately 5 hours 2

Despite these differences in absorption rates, all three formulations are bioequivalent in terms of overall drug exposure 2.

Clinical Implications

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

• Allows for once-daily dosing with the XL formulation 3
• Steady-state plasma concentrations are typically reached within 8 days of starting treatment 1
• The extended half-life of the metabolites means they accumulate to higher concentrations than the parent drug during chronic dosing 1
• When discontinuing bupropion, a gradual tapering approach is recommended to minimize withdrawal symptoms 3

Factors Affecting Half-Life

Several factors can influence the half-life and metabolism of bupropion:

• Hepatic impairment: May prolong half-life and increase drug exposure 3
• Renal impairment: Requires dose adjustment, with half the normal dose recommended for moderate to severe renal impairment 3
• Drug interactions: Medications affecting CYP2B6 (the primary enzyme responsible for forming hydroxybupropion) may alter bupropion metabolism 3, 1

Understanding the half-life of bupropion and its metabolites is essential for appropriate dosing, monitoring for drug interactions, and managing treatment discontinuation.