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首页> 外文期刊>Journal of applied toxicology >QT prolongation in guinea pigs for preliminary screening of torsadogenicity of drugs and drug-candidates. II.
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QT prolongation in guinea pigs for preliminary screening of torsadogenicity of drugs and drug-candidates. II.

机译：豚鼠的QT延长，用于初步筛选药物和候选药物的致畸性。二。

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Experimental approaches on anaesthetised guinea pigs have been shown recently to be satisfactorily predictive of the torsadogenic risk of drugs. This work aimed at obtaining additional data, for a further understanding of the reliability and/or the limits of this model. Clonidine (non-torsadogenic in humans) induced a lengthening of the ECG parameter of RR in anaesthetised guinea pigs, without any corresponding increase of QT (corrected by the algorithms of Bazett and Fridericia). Thus, 'QT correct' prolonging effects produced by drugs torsadogenic in humans, on the guinea pig model are primarily due to inhibition of cardiac repolarisation. The corresponding RR prolongation is a consequence (not the cause) of this primary effect. Astemizole, haloperidol and terfenadine, torsadogenic in humans, produced in Langendorff perfused guinea pig hearts a prolongation of the QT interval. Chlorprotixene (non-torsadogenic) did not produce any significant effect on QT. These results are fully consistent with previous observations in anaesthetised guinea pigs. In Langendorff perfused hearts, pentobarbital does not affect cardiac repolarisation and does not potentiate the QT-prolonging effect of astemizole. Together with the findings reported by many authors, these data suggest that ECG recording in anaesthetised guinea pigs is a reliable model for cardiac safety studies evaluating the influence of drugs on the repolarisation process.
机译：最近已经证明，在麻醉的豚鼠上进行实验的方法可以令人满意地预测药物的致畸风险。这项工作旨在获取其他数据，以进一步了解此模型的可靠性和/或限制。可乐定（在人类中无致畸性）在麻醉的豚鼠中引起RR的ECG参数延长，而QT却没有相应增加（通过Bazett和Fridericia的算法校正）。因此，人为致源性药物在豚鼠模型上产生的“ QT校正”延长效应主要是由于抑制了心脏复极。相应的RR延长是这种主要作用的结果（而非原因）。在Langendorff灌注的豚鼠心脏中产生的具有人类致畸性的阿斯咪唑，氟哌啶醇和特非那定延长了QT间隔。氯丙ix烯（非托沙地平）对QT没有产生任何显着影响。这些结果与先前在麻醉的豚鼠中的观察结果完全一致。在Langendorff灌注心脏中，戊巴比妥不会影响心脏复极，也不会增强阿司咪唑的QT延长作用。结合许多作者报告的发现，这些数据表明，在麻醉的豚鼠中进行ECG记录是评估药物对复极化过程影响的心脏安全性研究的可靠模型。

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