HEMODYNAMIC AND ELECTROPHYSIOLOGICAL EFFECTS OF MITEMCINAL (GM-611), A NOVEL PROKINETIC AGENT DERIVED FROM ERYTHROMYCIN IN A HALOTHANE-ANESTHETIZED CANINE MODEL
スポンサーリンク
概要
- 論文の詳細を見る
Mitemcinal (GM-611) is a novel erythromycin-derived prokinetic agent that acts as an agonist at the motilin receptor. We investigated the QT-prolonging effects of mitemcinal using a halothane-anesthetized canine model. Intravenous administration of mitemcinal at doses of more than 8.3 mg/ kg per 10 min significantly prolonged the QT interval corrected by Fridericia's corrections. Mitemcinal exhibited a bradycardiac effect and produced significantly greater prolongation in monophasic action potential duration (MAP_<90>) at sinus rhythm compared with MAP90 at pacing and showed reverse usedependent prolongation of repolarization, suggesting that the negative chronotropic effect of mitemcinal potentiates the prolongation of the repolarization period. A technique using MAP/pacing electrodes allowed measurements of both MAP_<90> and effective refractory period (ERP) simultaneously at the same ventricular site. Although mitemcinal slightly prolonged the MAP_<90(CL400)> and ERP in comparison with the control group at the dose of 25 mg/kg per 10 min, the terminal repolarization period, the difference between MAP_<90(CL400)> and ERP, did not increase suggesting the absence of a proarrhythmic effect even with a 7000-fold for the therapeutic blood concentration as free level. The electrophysiological results from mitemcinal in this study indicate that the risk of serious arrhythmia such as torsades de pointes, a major clinical concern related to QT interval prolongation, might be low.
- 日本トキシコロジー学会の論文
- 2007-08-17
著者
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Omura Satoshi
The Kitasato Institute, Kitasato Institute for Life Sciences and Graduate School of Infection Contro
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鈴木 雅実
Safety Assessment Dep. Fuji Gotemba Res. Laboratories Chugai Pharmaceutical Co. Ltd.
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鈴木 雅実
Safety Assessment Department Chugai Pharmaceutical Co. Ltd.
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Kato Atsuhiko
中外製薬富士御殿場研究所
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Kato Atsuhiko
Fuji-gotemba Research Laboratories Chugai Pharmaceutical Co. Ltd.
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Suzuki Masami
中外製薬富士御殿場研究所
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KIMURA Kazuya
Safety Assessment Department, Chugai Pharmaceutical Co., Ltd.
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Tabo Mitsuyasu
Safety Assessment Department Chugai Pharmaceutical Co. Ltd.
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Tabo Mitsuyasu
Safety Assessment Department Chugai Pharmaceutical Co. Ltd.:laboratory Of Pharmacology Graduate Scho
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Kimura Kazuya
Japan Pharmaceutical Manufacturers Assoc. Drug Evaluation Committee Non-clinical Evaluation Subcommi
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Kimura Kazuya
Fuji Gotemba Research Laboratories Chugai Pharmaceutical Co. Ltd.
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鈴木 雅実
Fuji Gotemba Research Laboratories Chugai Pharmaceutical Co. Ltd.
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Omura Satoshi
The Kitasato Institute
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KIMURA Kazuya
Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd.
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TABO Mitsuyasu
Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd.
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MIZOGUCHI Keiji
Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd.
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SUZUKI Masami
Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd.
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ITOH Zen
Gunma University
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TAKANASHI Hisanori
Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd.
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Tabo Mitsuyasu
Fuji Gotemba Research Laboratories Chugai Pharmaceutical Co. Ltd.
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Mizoguchi Keiji
Research Compliance & Quality Assurance Coordination Fuji Gotemba Research Laboratories Chugai P
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Mizoguchi Keiji
Fuji-gotemba Research Laboratories Chugai Pharmaceutical Co. Ltd.
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Mizoguchi Keiji
Toxicology Laboratory Chugai Pharmaceutical Co. Ltd.
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Omura Satoshi
The Kitasato Inst.
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Kato Atsuhiko
Safety Assessment Laboratory Chugai Pharmaceutical Co. Ltd.
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Takanashi Hisanori
Fuji-gotemba Research Laboratories Chugai Pharmaceutical Co. Ltd.
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