Norepinephrine + dopamine reuptake inhibitor with nicotinic-ACh-receptor antagonism (mechanism behind smoking-cessation indication). Active hydroxybupropion metabolite contributes. No sexual side effects and mild weight-neutral-to-loss profile → often chosen when SSRI sexual dysfunction is a problem.
Half-Life (t½)
PO: 14h
Dosing Guidelines
PO: Typical 250 mg (Range: 150–450 mg)
Target Organ Systems
nervous
Interactions
Atomoxetine (major): CYP2D6 inhibition (bupropion + OH-bupropion). Todor 2016 (PMID:27518170) sequential open-label, atomoxetine 25 mg single ± bupropion 300 mg × 7d: AUC0-∞ 1580→8060 ng·h/mL (5.1×); main metabolite −1.5×. Ki ≈ 1/4.1 = 0.244 µM at combined Cp_perp ≈ 1 µM. >5× AUC qualifies as strong CYP2D6 inhibition.
Desipramine (major): CYP2D6 inhibition (mechanistic). Reese 2008 (PMID:18420781) DMD mechanistic abstract verbatim "marked (5-fold) increases in desipramine exposure" (refers to clinical DDI). Threohydro/erythrohydrobupropion in-vitro Ki 1.7-5.4 µM at CYP2D6 explains the 5-fold clinical bump. Ki ≈ 1/4 = 0.25 µM. TCA cardiac/CNS toxicity — dose reduction.