What are the half-lives of Bupropion (Immediate Release) IR, (Sustained Release) SR, and (Extended Release) XL?

Half-Life of Bupropion Formulations: IR vs SR vs XL

The mean elimination half-life of bupropion is 21 (±9) hours across all formulations, but the absorption rates differ significantly with immediate release (IR) reaching peak plasma concentrations in approximately 1.5 hours, sustained release (SR) in approximately 3 hours, and extended release (XL) in approximately 5 hours. 1, 2

Pharmacokinetic Differences Between Formulations

Immediate Release (IR)

• Peak plasma concentration (Tmax): ~1.5 hours 2
• Dosing frequency: Three times daily 2
• Initial (alpha) phase half-life: ~1.5 hours 3
• Terminal (beta) phase half-life: ~14 hours 3

Sustained Release (SR)

• Peak plasma concentration (Tmax): ~3 hours 2
• Dosing frequency: Twice daily 2
• Elimination half-life: 21 (±9) hours (same as other formulations) 1
• Typical dosing: Starting dose 150 mg/day, maximum 450 mg/day 4

Extended Release (XL)

• Peak plasma concentration (Tmax): ~5 hours 1, 2
• Dosing frequency: Once daily 2
• Elimination half-life: 21 (±9) hours (same as other formulations) 1
• Prolonged absorption compared to IR and SR formulations 2

Bioequivalence and Metabolites

All three formulations (IR, SR, and XL) are bioequivalent in terms of:

• Peak plasma concentration (Cmax)
• Area under the curve (AUC)
• Overall systemic exposure to bupropion and its three active metabolites 2, 5

The primary difference between formulations is not in the elimination half-life but in the absorption rate, which affects the dosing frequency and peak concentration timing.

Active Metabolites

Bupropion is extensively metabolized in the liver, producing three active metabolites:

1. Hydroxybupropion:

   • Primary active metabolite
   • Half-life: ~20 hours
   • At steady state, Cmax is 4-7 times higher than parent drug
   • AUC approximately 10-fold greater than bupropion
   • Approximately 50% as active as bupropion 1, 2

2. Threohydrobupropion:

   • Half-life: ~37 (±13) hours
   • Cmax approximately 5-fold greater than bupropion
   • Approximately 20% as active as bupropion 1, 2

3. Erythrohydrobupropion:

   • Half-life: ~33 (±10) hours
   • Cmax similar to bupropion
   • Approximately 20% as active as bupropion 1, 2

Clinical Implications

• The longer half-lives of the metabolites (particularly threohydrobupropion and erythrohydrobupropion) contribute to the overall therapeutic effect beyond what would be expected from the parent compound alone.
• The extended-release formulation (XL) allows for once-daily dosing despite the unchanged elimination half-life of the parent compound, due to its modified absorption profile.
• No dosage adjustments are necessary between smokers and non-smokers as smoking status does not significantly affect bupropion pharmacokinetics 6.

Common Pitfalls and Caveats

• Despite similar elimination half-lives across formulations, they are not interchangeable in terms of dosing frequency due to differences in absorption profiles.
• The therapeutic effects of bupropion depend not only on the parent drug but also on its active metabolites, which have longer half-lives than bupropion itself.
• When switching between formulations, bioequivalent doses should be used to maintain therapeutic effect.
• In patients with moderate to severe hepatic or renal impairment, dose adjustments may be necessary regardless of formulation 7.