Prediction of drug-induced QT interval prolongation in telemetered common marmosets
スポンサーリンク
概要
- 論文の詳細を見る
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.
- 日本トキシコロジー学会の論文
- 2008-08-01
著者
-
TABO Mitsuyasu
Safety Assessment Department, Chugai Pharmaceutical Co., Ltd.
-
Tabo Mitsuyasu
Safety Assessment Department Research Division Chugai Pharmaceutical Co. Ltd.
-
Kobayashi Kazuko
中外製薬
-
Kobayashi Kazuko
Research Compliance & Quality Assurance Coordination Department Research Division Chugai Pharmac
-
Kimura Kazuya
Safety Assessment Dep. Chugai Pharmaceutical Co. Ltd.
-
SHISHIDO Nobuyuki
Safety Assessment Department
-
NAKANO Kounosuke
Pre-clinical Research Department
-
Hara Toshiko
Safety Assessment Department Research Division Chugai Pharmaceutical Co. Ltd.
-
Tabo Mitsuyasu
Safety Assessment Dep. Chugai Pharmaceutical Co. Ltd.
-
Sone Sachiko
Safety Assessment Department, Research Division, Chugai Pharmaceutical Co., Ltd.
-
Kuramoto Shino
Pre-clinical Research Department, Research Division, Chugai Pharmaceutical Co., Ltd.
-
Onodera Hideko
Research Compliance & Quality Assurance Coordination Department, Research Division, Chugai Pharmaceu
-
Sone Sachiko
Safety Assessment Department Research Division Chugai Pharmaceutical Co. Ltd.
-
Kuramoto Shino
Pre-clinical Research Department Research Division Chugai Pharmaceutical Co. Ltd.
-
Onodera Hideko
Research Compliance & Quality Assurance Coordination Department Research Division Chugai Pharmac
-
Nakano Kohnosuke
Pre-clinical Research Department Research Division Chugai Pharmaceutical Co. Ltd.
-
Nakano Kounosuke
Pre-clinical Research Department Research Division Chugai Pharmaceutical Co. Ltd. Fuji Gotemba Resea
-
Shishido Nobuyuki
Safety Assessment Department Research Division Chugai Pharmaceutical Co. Ltd.
-
Shishido Nobuyuki
Safety Assessment Department Research Division Chugai Pharmaceutical Co. Ltd. Fuji Gotemba Research
-
Kobayashi Kazuko
Research Compliance & Quality Assurance Coordination Department Research Division Chugai Pharmac
関連論文
- Accurate detection of drug-induced delayed ventricular repolarization with a suitable correction formula in Langendorff guinea pig heart
- Accurate detection of drug-induced delayed ventricular repolarization with a suitable correction formula in Langendorff guinea pig heart
- EFFECT OF DOSE REGIMEN ON THE TOXICITY OF 2'-DEOXY-2'-METHYLIDENECYTIDINE (DMDC) IN MONKEYS
- RELATIONSHIP BETWEEN AUC of 5'-DFUR AND TOXICITY OF CAPECITABINE, FLUOROPYRIMIDINE CARBAMATE ANALOGS, AND 5'-DFUR IN MONKEYS, MICE, AND RATS
- 21D-04-5 Effect on male reproductive organs and lymph nodes in dogs treated for long period with L-dopa and decarboxylase inhibitor.
- Toxicological assessment of a novel anti-tumor agent Capecitabine (Ro 09-1978, 5'-DFCR derivative : Species differences and improvement of intestinal toxicity
- 108 TOXICOLOGICAL EFFECT OF COMBINATION TREATMENT WITH INTERFERON alpha A/D AND 5'-DEOXY-5 FLUOROURIDIN (5'-DFUR) IN HCT116 AND WIDIR-BEARING AND TUMOR-FREE NUDE MICE
- QT-RR RELATIONSHIPS AND SUITABLE QT CORRECTION FORMULAS FOR HALOTHANE-ANESTHETIZED DOGS
- Effects of QT prolongation drugs on the QT interval under pacing condition in anesthetized dogs (CIRCULATORY SYSTEM) (GENERAL SESSION BY POSTER PRESENTATION) (Proceedings of the 30th Annual Meeting)
- Effects of drugs associated with QT prolongation on monophasic action potential duration in anesthetized guinea-pigs. (CIRCULATORY SYSTEM) (GENERAL SESSION BY POSTER PRESENTATION) (Proceedings of the 30th Annual Meeting)
- QT PRODACT : Evaluation of the Potential of Compounds to Cause QT Interval Prolongation by Action Potential Assays Using Guinea-Pig Papillary Muscles
- QT PRODACT : Inter- and Intra-facility Variability of the Action Potential Assay Using Isolated Guinea-Pig Papillary Muscles
- QT PRODACT : A Multi-site Study of In Vitro Action Potential Assays on 21 Compounds in Isolated Guinea-Pig Papillary Muscles
- Prediction of drug-induced QT interval prolongation in telemetered common marmosets
- Evaluation of drug-induced QT prolongation in conscious marmosets(Circulatory system, Proceedings of the 32nd Annual Meeting)
- P8-07 QT Interval Prolongation : Project for Database Construction, 1) Standard Protocol, and Inter- and Intra-Facility Differences in APD Assay Using Isolated Guinea Pig Papillary Muscles(CIRCULATORY SYSTEM-2/ACTIVE OXYGEN)(GENERAL SESSION BY POSTER PRES
- P8-08 QT Interval Prolongation : Project for Database Construction, 2) The Usefulness of APD Study in Isolated Guinea Pig Papillary Muscles-Comparison with hERG study and canine Purkinje fiber APD study(CIRCULATORY SYSTEM-2/ACTIVE OXYGEN)(GENERAL SESSION
- COMPARATIVE TOXICOLOGICAL ASSESSMENT OF A WATER-SOLUBLE AZOLE ADMINISTERED BOTH ORALLY AND BY INTRAVENOUS CONTINUOUS INFUSION IN CYNOMOLGUS MONKEYS
- Comparison of in vitro metabolic conversion of capecitabine to 5-FU in rats, mice, monkeys and humans - toxicological implications
- 21D-02-1 COX-2 Inhibition may participate in The Decrease of Renal Blood Flow induced by NSAIDs.
- 21D-01-1 In vitro nephrotoxicity assay system and its application to high throughput screening
- Electrophysiological Characterization of Cardiomyocytes Derived From Human Induced Pluripotent Stem Cells
- Comparison of in vitro metabolic conversion of capecitabine to 5-FU in rats, mice, monkeys and humans - toxicological implications
- Electrophysiological Characterization of Cardiomyocytes Derived From Human Induced Pluripotent Stem Cells