Comprehensive and rigorous analysis of drug-induced QT interval prolongation in anesthetized guinea pigs using 11 antihistamines with clinical reports on adverse drug reactions

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  • 薬物性QT延長症候群に関連した有害事象が報告されている抗ヒスタミン薬11種の非臨床試験による網羅的な心臓電気生理学的作用の評価

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<p>Guiding principle in the use of antihistamines for patients with long QT syndrome (LQTs) has not been sufficiently discussed, although suspected adverse drug reactions (ADR) relating to drug-induced LQTs were reported in some antihistamines. To clarify the causality between ADR and each drug, we exhaustively assessed the electro-pharmacological properties of 11 antihistamines with ADR reports by using anesthetized guinea-pig model under the monitoring of ECG parameters and monophasic action potential duration (MAP90) of the right ventricle. Cetirizine, clemastine, diphenhydramine, ebastine, epinastine, fexofenadine, hydroxyzine, levocetirizine, loratadine, mequitazine, and promethazine were administered intravenously. Diphenhydramine and hydroxyzine at therapeutic dose and clemastine at 10 times higher therapeutic dose prolonged the QT interval and MAP90. On the other hand, other 8 antihistamines did not prolong the QT interval nor MAP90 even though they were administered at 10 times higher therapeutic dose.  These data indicated that diphenhydramine, hydroxyzine, and clemastine essentially have a potential to be a causative drug of drug-induced LQTs, whereas the cases using other 8 antihistamines should be reinvestigated on the case information such as the presence of cardiovascular diseases and concomitant medications.</p>

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