Pharmacokinetic-Pharmacodynamic Analysis of the Electrocardiographic Effects of Terfenadine and Quinidine in Rats
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概要
- 論文の詳細を見る
In establishing a method of electrocardiographic (ECG) measurement for investigating drug-induced ECG changes, we examined the ECG effects and pharmacokinetics of terfenadine (TFN) and quinidine (QND) in rats. The time profiles of the plasma concentration and ECG parameters, such as the QT interval determined from limb lead II (QT-II) and the precordial chest lead (QT-V), heart rate and PR interval, were examined during constant intravenus infusion of TFN (5 or 15 mg/kg/h) or QND sulfate dihydrate (10 or 30 mg/kg/h). Both agents provided significant and concentration-dependent QT prolongation. The plasma concentrations (C-<10>), where 10 ms of QT prolongation was observed, were 1.03 μM for TFN and 5.12 μM for QND, respectively. The calculated plasma unbound concentration of C_<10> (C_<10・f>) was 10.3 nM for TFN and 3.82 μM for QND, which coincides with previously reported in vitro values of IC_<50> for potassium channels. The drug-induced QT prolongation was quantitatively reproduced in rats within the clinical concentration range. The usefulness of our methodology for the evaluation of arrhythmogenic hazards of the drugs was also demonstrated.
- 公益社団法人日本薬学会の論文
- 1996-09-15
著者
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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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IGA Tatsuji
International University of Health and Welfare
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Yamamoto Koujirou
Department Of Pharmacy The University Of Tokyo Hospital Faculty Of Medicine The University Of Tokyo
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Yamamoto Koujirou
Department Of Pharmacy The Gunma University Hospital Gunma University School Of Medicine:department
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Yamamoto Koujirou
Department Of Clinical Pharmacology Gunma University School Of Medicine
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Yamamoto Koujirou
Department Of Clinical Pharmacology Gunma University Graduate School Of Medicine
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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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SAWADA Yasufumi
(Present address)Faculty of Pharmaceutical Sciences, Kyushu University
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HANADA Erika
Department of Pharmacy, The University of Tokyo Hospital, Faculty of Medicine, The University of Tok
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Hanada Erika
Department Of Pharmacy The University Of Tokyo Hospital Faculty Of Medicine The 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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Yamano Katsuhiro
Biopharmaceutical And Pharmacokinetic Research Laboratories Fujisawa Pharmaceutical Co. Ltd.
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