Prediction of drug-induced QT interval prolongation in telemetered common marmosets
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- Tabo Mitsuyasu
- Safety Assessment Department, Research Division, Chugai Pharmaceutical Co., Ltd.
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- Hara Toshiko
- Safety Assessment Department, Research Division, Chugai Pharmaceutical Co., Ltd.
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- Sone Sachiko
- Safety Assessment Department, Research Division, Chugai Pharmaceutical Co., Ltd.
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- Shishido Nobuyuki
- Safety Assessment Department, Research Division, Chugai Pharmaceutical Co., Ltd.
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- Kuramoto Shino
- Pre-clinical Research Department, Research Division, Chugai Pharmaceutical Co., Ltd.
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- Nakano Kounosuke
- Pre-clinical Research Department, Research Division, Chugai Pharmaceutical Co., Ltd.
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- Onodera Hideko
- Research Compliance & Quality Assurance Coordination Department, Research Division, Chugai Pharmaceutical Co., Ltd.
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- Kimura Kazuya
- Safety Assessment Department, Research Division, Chugai Pharmaceutical Co., Ltd.
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- Kobayashi Kazuko
- Research Compliance & Quality Assurance Coordination Department, Research Division, Chugai Pharmaceutical Co., Ltd.
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抄録
Drug-induced QT interval prolongation is a critical issue in development of new chemical entities, so the pharmaceutical industry needs to evaluate risk as early as possible. Common marmosets have been in the limelight in early-stage development due to their small size, which requires only a small amount of test drug. The purpose of this study was to determine the utility of telemetered common marmosets for predicting drug-induced QT interval prolongation. Telemetry transmitters were implanted in common marmosets (male and female), and QT and RR intervals were measured. The QT interval was corrected for the RR interval by applying Bazett’s and Fridericia’s correction formulas and individual rate correction. Individual correction showed the least slope for the linear regression of corrected QT (QTc) intervals against RR intervals, indicating that it dissociated changes in heart rate most effectively. With the individual correction method, the QT-prolonging drugs (astemizole, dl-sotalol) showed QTc interval prolongations and the non-QT-prolonging drugs (dl-propranolol, nifedipine) did not show QTc interval prolongations. The plasma concentrations of astemizole and dl-sotalol associated with QTc interval prolongations in common marmosets were similar to those in humans, suggesting that the sensitivity of common marmosets would be appropriate for evaluating risk of drug-induced QT interval prolongation. In conclusion, telemetry studies in common marmosets are useful for predicting clinical QT prolonging potential of drugs in early stage development and require only a small amount of test drug.
収録刊行物
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- The Journal of Toxicological Sciences
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The Journal of Toxicological Sciences 33 (3), 315-325, 2008
一般社団法人 日本毒性学会
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詳細情報 詳細情報について
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- CRID
- 1390282679876807424
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- NII論文ID
- 110006862208
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- NII書誌ID
- AN00002808
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- ISSN
- 18803989
- 03881350
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- NDL書誌ID
- 9609188
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
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- 抄録ライセンスフラグ
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