Effect of Amiodarone on the Serum Concentration/Dose Ratio of Metoprolol in Patients with Cardiac Arrhythmia

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著者

    • FUKUMOTO Kyoko
    • Department of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences
    • KOBAYASHI Takashi
    • Department of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences
    • TACHIBANA Kanako
    • Department of Clinical Pharmacology & Pharmacokinetics, Osaka University of Pharmaceutical Sciences
    • KATO Ryuji
    • Department of Clinical Pharmacology & Pharmacokinetics, Osaka University of Pharmaceutical Sciences
    • TANAKA Kazuhiko
    • Department of Clinical Pharmacology & Pharmacokinetics, Osaka University of Pharmaceutical Sciences
    • UENO Kazuyuki
    • Department of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences

抄録

  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>

収録刊行物

  • Drug metabolism and pharmacokinetics  

    Drug metabolism and pharmacokinetics 21(6), 501-505, 2006-12-25 

    The Japanese Society for the Study of Xenobiotics

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各種コード

  • NII論文ID(NAID)
    10018659065
  • NII書誌ID(NCID)
    AA1162652X
  • 本文言語コード
    ENG
  • 資料種別
    SHO
  • ISSN
    13474367
  • データ提供元
    CJP書誌  J-STAGE 
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