000075913 001__ 75913
000075913 005__ 20210121114448.0
000075913 0247_ $$2doi$$a10.1016/j.jelectrocard.2015.08.004
000075913 0248_ $$2sideral$$a92981
000075913 037__ $$aART-2015-92981
000075913 041__ $$aeng
000075913 100__ $$0(orcid)0000-0001-9963-1205$$aVicente, J.
000075913 245__ $$aSex differences in drug-induced changes in ventricular repolarization
000075913 260__ $$c2015
000075913 5060_ $$aAccess copy available to the general public$$fUnrestricted
000075913 5203_ $$aIntroduction: Heart rate corrected QT (QTc) interval prolongation is a predictor of drug-induced torsade de pointes, a potentially fatal ventricular arrhythmia that disproportionately affects women. This study assesses whether there are sex differences in the ECG changes induced by four different hERG potassium channel blocking drugs.
Methods and results: Twenty-two healthy subjects (11 women) received a single oral dose of dofetilide, quinidine, ranolazine, verapamil and placebo in a double-blind 5-period crossover study. ECGs and plasma drug concentrations were obtained at pre-dose and at 15 time-points post-dose. Dofetilide, quinidine and ranolazine prolonged QTc. There were no sex differences in QTc prolongation for any drug, after accounting for differences in exposure. Sex differences in any ECG biomarker were observed only with dofetilide, which caused greater J-Tpeakc prolongation (p=0.045) but lesser Tpeak-Tend prolongation (p=0.006) and lesser decrease of T wave amplitude (p=0.003) in women compared to men.
Conclusions: There were no sex differences in QTc prolongation for any of the studied drugs. Moreover, no systematic sex differences in other drug-induced ECG biomarker changes were observed in this study. This study suggests that the higher torsade risk in women compared to men is not due to a larger concentration-dependent QTc prolongation.
000075913 536__ $$9info:eu-repo/grantAgreement/ES/DGA/FSE$$9info:eu-repo/grantAgreement/ES/DGA/Grupo Consolidado BSICoS$$9info:eu-repo/grantAgreement/ES/MINECO/TIN2013-41998-R
000075913 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
000075913 590__ $$a1.29$$b2015
000075913 591__ $$aCARDIAC & CARDIOVASCULAR SYSTEMS$$b93 / 124 = 0.75$$c2015$$dQ3$$eT3
000075913 592__ $$a0.559$$b2015
000075913 593__ $$aCardiology and Cardiovascular Medicine$$c2015$$dQ2
000075913 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion
000075913 700__ $$aJohannesen, L.
000075913 700__ $$aMason, J. W.
000075913 700__ $$0(orcid)0000-0002-1960-407X$$aPueyo, E.$$uUniversidad de Zaragoza
000075913 700__ $$aStockbridge, N.
000075913 700__ $$aStrauss, D. G.
000075913 7102_ $$15008$$2800$$aUniversidad de Zaragoza$$bDpto. Ingeniería Electrón.Com.$$cÁrea Teoría Señal y Comunicac.
000075913 773__ $$g48, 6 (2015), 1081-1087$$pJ. electrocardiol.$$tJOURNAL OF ELECTROCARDIOLOGY$$x0022-0736
000075913 8564_ $$s405657$$uhttps://zaguan.unizar.es/record/75913/files/texto_completo.pdf$$yPostprint
000075913 8564_ $$s41853$$uhttps://zaguan.unizar.es/record/75913/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint
000075913 909CO $$ooai:zaguan.unizar.es:75913$$particulos$$pdriver
000075913 951__ $$a2021-01-21-10:44:08
000075913 980__ $$aARTICLE