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Remdesivir (VEKLURY) for treating COVID-19: Guinea pig ex vivo and in vivo cardiac electrophysiological effects

J Cardiovasc Pharmacol. 2022 Jun 27. doi: 10.1097/FJC.0000000000001321. Online ahead of print.


Bradycardia and QTc interval prolongation on the ECG have been reported with remdesivir (Veklury®), an antiviral drug recently approved for treating severely ill COVID-19 patients. 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 monophasic action potential duration measured at 90% repolarization (MAPD90). 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 MAPD90, while pacing the hearts at basic stimulation cycle lengths of 200 or 250 ms, 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 MAPD90-prolonging effects of dofetilide 20 nmol/L (n=4) hearts). In vivo remdesivir caused small but statistically significant prolongations of the RR and QTcF 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 COVID-19 patients concomitantly treated with multiple drugs.

PMID:35881906 | DOI:10.1097/FJC.0000000000001321

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