Açıklama
Bupropion is a potent CYP2D6 inhibitor that substantially increases metoprolol plasma concentrations, potentially causing excessive beta-blockade (bradycardia, hypotension, heart block).
Mekanizma
Metoprolol is primarily metabolised by CYP2D6 to inactive alpha-hydroxy metoprolol; bupropion's potent CYP2D6 inhibition reduces first-pass and systemic clearance, raising metoprolol AUC by 4- to 5-fold in extensive metabolisers.
Klinik Önemi
Pharmacokinetic studies demonstrate marked metoprolol accumulation; case reports describe bradycardia and symptomatic hypotension requiring metoprolol dose reduction.
Yönetim
Reduce metoprolol dose when starting bupropion; monitor heart rate and blood pressure; consider switching to atenolol (not CYP2D6-metabolised) if excessive bradycardia occurs.