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Remdesivir (VEKLURY) for Treating COVID-19: Guinea Pig Ex Vivo and In Vivo Cardiac Electrophysiological Effects.
Pilote, Sylvie; Simard, Chantale; Drolet, Benoit.
  • Pilote S; Institut universitaire de cardiologie et de pneumologie de Québec, Centre de recherche, Chemin Sainte-Foy, Québec, Canada; and.
  • Simard C; Institut universitaire de cardiologie et de pneumologie de Québec, Centre de recherche, Chemin Sainte-Foy, Québec, Canada; and.
  • Drolet B; Faculté de pharmacie, Université Laval, Québec, Canada.
J Cardiovasc Pharmacol ; 80(4): 616-622, 2022 10 01.
Article in English | MEDLINE | ID: covidwho-2051608
ABSTRACT
ABSTRACT Bradycardia and QTc interval prolongation on the ECG have been reported with remdesivir (Veklury), an antiviral drug recently approved for treating severely ill patients with COVID-19. The objective was to evaluate the effects of remdesivir on cardiac electrophysiology ex vivo and in vivo. Ex vivo Langendorff retroperfusion experiments were performed on isolated hearts from male Hartley guinea pigs (n = 23, total) exposed to either remdesivir 3, 10, or 30 µmol/L to assess drug-induced prolongation of the monophasic action potential duration measured at 90% repolarization (MAPD 90 ). In vivo ECG recordings using wireless cardiac telemetry were performed in guinea pigs (n = 6) treated with daily i.p. doses of remdesivir 5 mg/kg on day 1 and 2.5 mg/kg on days 2-10. Ex vivo remdesivir (3, 10, and 30 µmol/L) had no statistically significant effect on MAPD 90 , while pacing the hearts at basic stimulation cycle lengths of 200 or 250 milliseconds, or when the hearts were not paced and beating at their intrinsic heart rate. In a second set of similar ex vivo experiments, remdesivir 10 µmol/L did not potentiate the MAPD 90 -prolonging effects of dofetilide 20 nmol/L (n = 4) hearts. In vivo remdesivir caused small but statistically significant prolongations of the RR and QTc F intervals at day 1 (5 mg/kg) and at day 10 (2.5 mg/kg). No ventricular arrhythmias were ever observed under the effect of remdesivir. Remdesivir causes bradycardia, and mild QTc prolongation, which nonetheless, could be of clinical relevance in many hospitalized patients with COVID-19 concomitantly treated with multiple drugs.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Long QT Syndrome / COVID-19 Drug Treatment Type of study: Experimental Studies / Prognostic study Limits: Animals Language: English Journal: J Cardiovasc Pharmacol Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Long QT Syndrome / COVID-19 Drug Treatment Type of study: Experimental Studies / Prognostic study Limits: Animals Language: English Journal: J Cardiovasc Pharmacol Year: 2022 Document Type: Article