Concomitant Treatment with Proton Pump Inhibitors and Cephalosporins Does Not Enhance QT-Associated Proarrhythmia in Iso
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Concomitant Treatment with Proton Pump Inhibitors and Cephalosporins Does Not Enhance QT‑Associated Proarrhythmia in Isolated Rabbit Hearts Julian Wolfes1,3 · Christian Ellermann1 · Sophie Burde1 · Patrick Leitz1 · Nils Bögeholz1 · Kevin Willy1 · Michael Fehr2 · Lars Eckardt1 · Gerrit Frommeyer1
© Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Recent results from data mining analyses and reports of adverse drug events suggest a QT-prolonging drug–drug interaction resulting from the combination of distinct proton pump inhibitors and cephalosporins. Therefore, this study aimed at investigating the effect of the suspected QT-prolonging combinations of lansoprazole + ceftriaxone and esomeprazole + cefazolin, respectively. 26 hearts of New Zealand White rabbits were retrogradely perfused and paced at different cycle lengths. After generating baseline data, the hearts were assigned to two groups: In group 1, hearts were treated with 5 µM lansoprazole. Thereafter, 200 µM ceftriaxone was infused additionally. Group 2 was perfused with 10 µM esomeprazole followed by 250 µM cefazolin. In group 1, lansoprazole did not significantly alter QT intervals and A PD90. Additional treatment with ceftriaxone significantly shortened QT interval, APD90 and slightly reduced dispersion of repolarization compared to sole lansoprazole infusion. In group 2, esomeprazole led to a significant shortening of the QT interval without altering A PD90 or dispersion. Additional treatment with the antibiotic cefazolin further shortened QT interval, A PD90 and reduced the dispersion of repolarization. Incidence of ventricular arrhythmias was not significantly altered in both groups. This is the first experimental whole-heart study that investigated the impact of a concomitant treatment with proton pump inhibitors and cephalosporins. In contrast to previous reports, the combination of both agents did not cause QT prolongation but instead shortened QT interval and action potential duration. As a consequence, no triggered activity occurred in the presence of a stable dispersion of repolarization. Keywords PPI · Cephalosporin · Esomeprazole · Lansoprazole · Sudden cardiac death · Arrhythmia Abbreviations APD Action potential duration APD90 Action potential duration at 90%-repolarization CFN Cefazolin CFX Ceftriaxone Handling Editor: Dr. Dakshesh Patel. * Julian Wolfes [email protected] 1
Department of Cardiology II (Electrophysiology), University Hospital Münster, Albert‑Schweitzer‑Campus 1, 48149 Münster, Germany
2
University of Veterinary Medicine Hannover, Foundation, Bünteweg 9, 30559 Hannover, Germany
3
Klinik für Kardiologie II ‑ Rhythmologie, Universitätsklinikum Münster, Albert‑Schweitzer Campus 1, 48149 Münster, Germany
CL Cycle length DDI Drug–drug interaction ECG Electrocardiogram ERP Effective refractory period ESO Esomeprazole LNS Lansoprazole MAP Monophasic action potential PPI Proton pump inhibitors PRR Post-repolarization refractoriness SQTS Short QT syndrome VT
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