Abstract
Some non-anti-arrhythmic drugs delay cardiac repolarization, which can be measured as an increase in the QT interval. Delays in cardiac repolarization create an electrophysiological environment that favours the development of cardiac arrhythmias, which may lead to torsade de pointes, which can be fatal. As part of the clinical development of eltrombopag, a thorough QT(c) study was conducted to evaluate the effects of eltrombopag on cardiac repolarization at both therapeutic and supratherapeutic doses and to characterize the relationship between plasma eltrombopag concentrations and change in QT(c). This study found no clinically significant QT prolongation for eltrombopag when administered as 50 mg or 150 mg every day for 5 days. There were no safety or tolerability signals of clinical concern. A small incidence of ventricular premature beats was observed, but this was consistent with previously reported incidences in healthy volunteers without apparent heart disease. To evaluate the effect of eltrombopag on cardiac repolarization and to characterize the relationship between plasma eltrombopag concentrations and change in QT(c). This was a double-blind, placebo- and active-controlled, randomized, balanced four-period, crossover...Continue Reading
References
Mar 1, 1977·The American Journal of Cardiology·M BrodskyK M Rosen
Mar 1, 1982·British Heart Journal·M T ViitasaloA Eisalo
Jun 1, 1981·American Heart Journal·P A SobotkaK M Rosen
Aug 18, 2000·Cardiovascular Research·W HaverkampR Shah
May 31, 2003·Nature Reviews. Drug Discovery·Bernard Fermini, Anthony A Fossa
Nov 19, 2003·Journal of Clinical Psychopharmacology·Andrew SatlinHarald Pohlmann
Mar 5, 2004·The New England Journal of Medicine·Dan M Roden
Jun 18, 2004·The New England Journal of Medicine·Panagiotis Korantzopoulos, Konstantinos Siogas
Mar 1, 2007·Blood·Julian M JenkinsConnie L Erickson-Miller
Nov 30, 2007·The New England Journal of Medicine·John G McHutchisonUNKNOWN TPL102357 Study Group
Nov 30, 2007·The New England Journal of Medicine·James B BusselJulian M Jenkins
Nov 29, 2008·Stem Cells·Connie L Erickson-MillerJulian M Jenkins
Citations
Apr 9, 2013·Cancer Chemotherapy and Pharmacology·Siobhan HayesEkaterina Gibiansky
Mar 23, 2013·Clinical Drug Investigation·Arne RingJeffrey Friedman
Jul 21, 2011·Drugs·Karly P Garnock-Jones
Oct 22, 2014·Drugs·Celeste B Burness
Nov 8, 2011·Clinical Therapeutics·Yang Zhang, Jill M Kolesar
Jul 2, 2011·British Journal of Pharmacology·L NalosM A Vos
Mar 14, 2012·Journal of Thrombosis and Haemostasis : JTH·Y TomiyamaY Kanakura
Nov 12, 2013·Journal of Clinical Pharmacology·Atsushi SugiyamaYuji Kumagai
Mar 5, 2013·Expert Opinion on Pharmacotherapy·Edoardo G Giannini, Nezam H Afdhal
Jun 28, 2013·Journal of Pharmacological Sciences·Kazuhiro MatsuoAkira Takahara
Oct 15, 2013·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Jane L LiesveldYuhchyau Chen
Feb 24, 2015·Drugs·Paul L McCormack
May 7, 2016·Drugs·Celeste B BurnessKarly P Garnock-Jones
Oct 5, 2011·Clinical Drug Investigation·Jørgen MatzEgon Toft
Sep 2, 2018·Cancer Chemotherapy and Pharmacology·Vassilios AslanisTaoufik Ouatas