Metoprolol Dronedarone

Dronedarone increases the AUC of metoprolol in patients with a CYP2D6 extensive metaboliser phenotype. The increase in negative inotropic effects are modest at the recommended therapeutic dose of dronedarone. 

In a study, 44 healthy subjects (39 extensive and 5 poor CYP2D6 metabolisers) were given metoprolol 200 mg daily for 13 days. Concurrent dronedarone 800 mg, 1.2 g or 1.6 g daily from day 5 increased the AUC of metoprolol in a dose-dependent manner in the 39 subjects who were extensive metabolisers by 1.63-, 2.08- and 2.53-fold, respectively. In addition, eoneurrent use resulted in an additive dose-dependent negative in-otropie effeet. In eontrast, metoprolol plasma levels were not affected by dronedarone. ... 

Dronedarone is structurally related to amiodarone, which is known to inhibit the cytochrome P450 isoenzyme CYP2D6, by which metoprolol is metabolised (see Amiodarone + Beta blockers , p.246). This study also shows that dronedarone inhibits CYP2D6, effectively making extensive metabolisers into poor metabolisers. For more information on metaboliser status see Genetic factors , (p.4). 

A pharmacokinetic interaction is established, but its clinical relevance is uncertain. The negative inotropic effect of metoprolol was almost doubled by the addition of dronedarone 1.6 g daily, but at the anticipated therapeutic dose of 800 mg the effects were modest. Other beta blockers that are metabolised by CYP2D6 (see Table 22.1 , (p.833)) would be expected to interact similarly. 

Damy T, Pousset F, Caplain H, Hulot J-S, Lechat P Fliarmacokinetic and i armaccHjynamic interactions between metoprolol and dronedarone in extensive and poor CYKD6 metabolizers healthy subjects. Fundam Clin Pharmacol (2004) 18,113-23. 

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See also in sourсe #XX -- [ ]

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