Effect of Amiodarone on the Serum Concentration/Dose Ratio of Metoprolol in Patients with Cardiac Arrhythmia
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- FUKUMOTO Kyoko
- Department of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences
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- KOBAYASHI Takashi
- Department of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences
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- TACHIBANA Kanako
- Department of Clinical Pharmacology & Pharmacokinetics, Osaka University of Pharmaceutical Sciences
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- KATO Ryuji
- Department of Clinical Pharmacology & Pharmacokinetics, Osaka University of Pharmaceutical Sciences
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- TANAKA Kazuhiko
- Department of Clinical Pharmacology & Pharmacokinetics, Osaka University of Pharmaceutical Sciences
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- KOMAMURA Kazuo
- Research Institute, National Cardiovascular Center
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- KAMAKURA Shiro
- Departments of Cardiology, National Cardiovascular Center
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- KITAKAZE Masafumi
- Departments of Cardiology, National Cardiovascular Center
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- UENO Kazuyuki
- Department of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences
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Abstract
Amiodarone has pharmacokinetic interactions with a number of therapeutic drugs, including warfarin, phenytoin, flecainide, and cyclosporine. Metoprolol is mainly metabolized by CYP2D6, and desethylamiodarone, a metabolite of amiodarone, has a markedly greater inhibitory effect on CYP2D6 than amiodarone. Therefore, the goal of this study was to evaluate the effect of amiodarone and desethylamiodarone on the serum concentration/dose ratio (C/D) of metoprolol in 120 inpatients with cardiac arrhythmias that received either metoprolol and amiodarone (MET+AMD group, n=30) or metoprolol alone (MET group, n=90). The ratio of administered metoprolol was compared between the MET and the MET+AMD groups. The dose of metoprolol and patient age were significantly higher in the MET group when compared with the MET+AMD group (1.00±0.480 versus 0.767±0.418 mg/kg/day, p<0.050; 68.6±10.6 versus 57.6±14.1 years, p<0.001, respectively), but the C/D ratio was significantly lower in the MET group than in the MET+AMD group (90.8±64.0 versus 136±97.8, p<0.01). Furthermore, a significant correlation was found between the C/D ratio and desethylamiodarone concentration (n=30, r=0.371, p<0.01). The results suggest that there is a significant interaction between amiodarone and metoprolol via desethylamiodarone-induced inhibition of CYP2D6. Therefore, careful monitoring of metoprolol concentrations/bioactivity of CYP2D6 is required in the context of co-administration of amiodarone and metoprolol.<br>
Journal
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- Drug Metabolism and Pharmacokinetics
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Drug Metabolism and Pharmacokinetics 21 (6), 501-505, 2006
The Japanese Society for the Study of Xenobiotics
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Details
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- CRID
- 1390001205180220928
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- NII Article ID
- 10018659065
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- NII Book ID
- AA1162652X
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- ISSN
- 18800920
- 13474367
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- Text Lang
- en
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- Data Source
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- JaLC
- Crossref
- CiNii Articles
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- Abstract License Flag
- Disallowed