Prevention of Pazopanib-Induced Prolonged Cardiac Repolarization and Proarrhythmic Effects

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dc.contributor.authorAkman, Tulay
dc.contributor.authorErbas, Oytun
dc.contributor.authorAkman, Levent
dc.contributor.authorYilmaz, Ahmet U.
dc.date.accessioned2019-10-27T22:12:34Z
dc.date.available2019-10-27T22:12:34Z
dc.date.issued2014
dc.departmentEge Üniversitesien_US
dc.description.abstractBackground: Pazopanib (PZP) may induce prolonged cardiac repolarization and proarrhythmic effects, similarly to other tyrosine kinase inhibitors. Objectives: To demonstrate PZP-induced prolonged cardiac repolarization and proarrhythmic electrophysiological effects and to investigate possible preventive effects of metoprolol and diltiazem on ECG changes (prolonged QT) in an experimental rat model. Methods: Twenty-four Sprague-Dawley adult male rats were randomly assigned to 4 groups (n = 6). The first group (normal group) received 4 mL of tap water and the other groups received 100 mg/kg of PZP (Votrient (R) tablet) perorally, via orogastric tubes. After 3 hours, the following solutions were intraperitoneally administered to the animals: physiological saline solution (SP), to the normal group and to the second group (control-PZP+SP group); 1 mg/kg metoprolol (Beloc, Ampule, AstraZeneca), to the third group (PZP+metoprolol group); and 1 mg/kg diltiazem (Diltiazem, Mustafa Nevzat), to the fourth group (PZP+diltiazem group). One hour after, and under anesthesia, QTc was calculated by recording ECG on lead I. Results: The mean QTc interval values were as follows: normal group, 99.93 +/- 3.62 ms; control-PZP+SP group, 131.23 +/- 12.21 ms; PZP+metoprolol group, 89.36 +/- 3.61 ms; and PZP+diltiazem group, 88.86 +/- 4.04 ms. Both PZP+metoprolol and PZP+diltiazem groups had significantly shorter QTc intervals compared to the control-PZP+SP group (p < 0.001). Conclusion: Both metoprolol and diltiazem prevented PZP-induced QT interval prolongation. These drugs may provide a promising prophylactic strategy for the prolonged QTc interval associated with tyrosine kinase inhibitor use.en_US
dc.identifier.doi10.5935/abc.20140138en_US
dc.identifier.endpage409en_US
dc.identifier.issn0066-782X
dc.identifier.issue5en_US
dc.identifier.pmid25229355en_US
dc.identifier.startpage403en_US
dc.identifier.urihttps://doi.org/10.5935/abc.20140138
dc.identifier.urihttps://hdl.handle.net/11454/49500
dc.identifier.volume103en_US
dc.identifier.wosWOS:000346165900010en_US
dc.identifier.wosqualityQ4en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherArquivos Brasileiros Cardiologiaen_US
dc.relation.ispartofArquivos Brasileiros De Cardiologiaen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectArrhythmias, Cardiac / therapyen_US
dc.subjectPyrimidines / adverse effectsen_US
dc.subjectHeart Conduction System / physiologyen_US
dc.subjectHeart / physiologyen_US
dc.titlePrevention of Pazopanib-Induced Prolonged Cardiac Repolarization and Proarrhythmic Effectsen_US
dc.typeArticleen_US

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