A Comparative Pharmacodynamic Study of the Arrhymogenicity of Antidepressants, Fluvoxamine and Imipramine, in Guinea Pigs
スポンサーリンク
概要
- 論文の詳細を見る
Among several classes of antidepressants, tricyclic antidepressants are known to prolong QTc intervals (QT interval corrected by heart rate) in electrocardiograms, while selective serotonin uptake inhibitors (SSRI) are considered to be devoid of arrhythmogenicity. In this study, we aimed to compare the arrhythmogenic potencies of imipramine (IMI), a typical tricyclic antidepressant, and fluvoxamine (FLV), an SSRI, at therapeutic and supratherapeutic concentrations using guinea pigs in vivo. Guinea pigs were anesthetized, and IMI (10 and 20mg/kg/h) or FLV (20mg/kg/h) was intravenously administered for 90 minutes to obtain in time-courses of drug concentrations in plasma and the changes in the QTc intervals during and after the drug administration. IMI induced distinct QTc prolongation in a dose-dependent manner, while FLV prolonged QTc intervals only slightly. A pharmacokinetic-pharmacodynamic analysis revealed that the potency for QTs prolongation of IMI was 1.7-fold higher than that of FLV. Taking the therapeutic concentration into account, the clinical risk of FLV for QTc prolongation was suggested to be 5-fold lower than that of IMI. Therefore, this SSRI agent was suggested to be safer than the tricyclic antidepressant for patients with cardiac risk factors, including arrhythmia, or fo those taking other arrhythmogenic drugs concomitantly.
- 公益社団法人日本薬学会の論文
- 2001-05-01
著者
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SAWADA Yasufumi
Department of Pharmacy, The University of Tokyo Hospital, Faculty of Medicine, University of Tokyo
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OHTANI Hisakazu
Laboratory of Drug Informatics, Graduate School of Pharmaceutical Sciences, The University of Tokyo
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SAWADA Yasufumi
Laboratory of Drug Informatics, Graduate School of Pharmaceutical Sciences, The University of Tokyo
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Sawada Y
Department Of Pharmaceutics Graduate School Of Pharmacertical Sciences Kyushu University
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Sawada Yasufumi
Department Of Pharmacy The University Of Tokyo Hospital Faculty Of Medicine University Of Tokyo
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IGA Tatsuji
International University of Health and Welfare
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Sato H
Department Of Pharmacy University Of Tokyo Hospital Faculty Of Medicine University Of Tokyo
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Iga T
Department Of Pharmacy University Of Tokyo Hospital
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Iga Tatsuji
Department Of Biopharmaceutics Faculty Of Pharmaceutical Sciences Nagoya City University:department
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OHTANI Hisakazu
Department of Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kyushu University
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Iga T
Department Of Biopharmaceutics Faculty Of Pharmaceutical Sciences Nagoya City University:department
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Ohtani Hisakazu
Laboratory Of Drug Informatics Graduate School Of Pharmaceutical Sciences The University Of Tokyo
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