QT PRODACT : Sensitivity and Specificity of the Canine Telemetry Assay for Detecting Drug-Induced QT Interval Prolongation
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概要
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The purpose of this investigation was to define the sensitivity and specificity of the canine telemetry assay for detecting drug-induced QT interval prolongation. Data from twelve studies generated in the QT PRODACT project were used in this investigation. The study design was a 4 × 4 Latin square cross-over design and included the following drugs: MK-499, E-4031, terfenadine, haloperidol, cisapride, bepridil, propranolol, diphenhydramine, captopril, verapamil, amoxicillin, and ciprofloxacin. The estimated root squared error of the model, which estimated the slope of the QT-RR relationships for each animal, for all dogs during the pre-dosing period was 5.45%. Using the QT-RR model, the sensitivity and specificity in each cutoff value that judges QT prolongation were estimated based on the experiment errors and measurement errors in the 12 studies. When the cutoff value was 5%, the sensitivity in 10% prolongation was 0.978 and the specificity in 0% was 0.996. In conclusion, it was judged that a 5% cutoff value for changes in heart rate corrected QT interval using the canine telemetry assay is practical, and the sensitivity and specificity of the telemetry assay are very high when using the analytical method presented here. Based upon this information, the canine telemetry assay using the individual subject heart rate correction model is recommended as a sensitive test system for the in vivo assessment of risk for QT interval prolongation.
- 2005-12-31
著者
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Yamamoto Keiji
日本製薬工業協会
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Yamamoto Keiji
Development Research Center Takeda Pharmaceutical Co. Ltd.
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Yamamoto Keiji
Non-clinical Evaluation Subcommittee Drug Evaluation Committee Japan Pharmaceutical Manufactures Ass
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Nishi Yasuhiro
Tsukuba Safety Assessment Laboratories Banyu Pharmaceutical Co. Ltd.
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Sekiya Koji
Pharmacology & Toxicology Department Ina Research Inc.
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MIYAZAKI Hiroyasu
Tsukuba Safety Assessment Laboratories, Banyu Pharmaceutical Co., Ltd.
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WATANABE Hiroyuki
Biostatistics, Banyu Pharmaceutical Co., Ltd.
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KITAYAMA Tetsuya
Toxicological Research Laboratories, Kyowa Hakko Kogyo Co., Ltd.
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NISHIDA Masahiro
Tsukuba Safety Assessment Laboratories, Banyu Pharmaceutical Co., Ltd.
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SUGANAMI Hideki
Data Management & Biostatistics, Kowa Co., Ltd.
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KITAYAMA Tetsuya
Pharmaceutical Research Center Toxicological Research Laboratories, Kyowa Hakko Kogyo Co., Ltd.
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Yamamoto Keiji
Development Research Center Takeda Pharmaceutical Co.
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Yamamoto Keiji
Drug Safety Research Laboratories Tanabe Seiyaku Co. Ltd.
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Yano Koji
Drug Safety Research Laboratories Tanabe Seiyaku Co. Ltd.
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Kii Yoshihide
Safety Research Laboratories Dainippon Sumitomo Pharma Co. Ltd.
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Suganami Hideki
Biostatistics And Data Management Department Kowa Co. Ltd.
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Yamada Kiyoshi
Pharmaceutical Research Laboratories Toray Industries Inc.
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Kitayama Tetsuya
Pharmaceutical Research Center Toxicological Research Laboratories Kyowa Hakko Kogyo Co. Ltd.
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Suganami Hideki
Research Department Saitama Daiichi Pharmaceutical Co. Ltd.
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Miyazaki Hiroyasu
Tsukuba Safety Assessment Laboratories Banyu Pharmaceutical Co. Ltd.
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Nishida Masahiro
Tsukuba Safety Assessment Laboratories Banyu Pharmaceutical Co. Ltd.
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Watanabe Hiroyuki
Biostatistics Banyu Pharmaceutical Co. Ltd.
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Yamamoto Keiji
Non-clinical Evaluation Subcommittee Drug Evaluation Committee Japan Pharmaceutical Manufactures Ass
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