Chloroquine for treatment of COVID-19 - a pig in a poke?
| Autor: | Rob ter Heine, Koen p van Rhee, Dirk Jan A.R. Moes, Annemieke Vermeulen Windsant, Peter Pickkers, Quirijn de Mast, Judith van Paassen, Roger J. M. Brüggemann, Jannette Rahamat-Langedoen, Birgit C. P. Koch, Roland R.J. van Kimmenade, Jeroen Schouten, Florens Polderman, Rutger van Raalte, Frank L. van de Veerdonk, Tim Frenzel, Paul D van der Linden, Monique H. Reijers, Nils E van 't Veer, David M. Burger, Mara van Rossum, Thijs C.D. Rettig |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
Coronavirus disease 2019 (COVID-19) business.industry Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Incidence (epidemiology) QT interval Gastroenterology Pharmacokinetics Chloroquine Internal medicine Cardiac toxicity medicine In patient business medicine.drug |
| DOI: | 10.1101/2020.07.06.20147470 |
| Popis: | Structured abstractObjectiveChloroquine has been frequently administered for treatment of coronavirus disease 2019 but there are serious concerns about its efficacy and cardiac safety. Our objective was to investigate the pharmacokinetics and safety of chloroquine in hospitalized COVID-19 patients.DesignA prospective observational study.SettingDutch hospitalsPatientsPatients admitted to the hospital for treatment of COVID-19.InterventionsPharmacokinetic samplingMeasurementsThe plasma concentrations of chloroquine and desethylchloroquine and QTc time.Main ResultsA total of 83 patients were included. The median (IQR) plasma concentration chloroquine during treatment was 1.05 μmol/L (0.63 - 1.55 μmol/L). None of the patients reached exposure exceeding the concentration to inhibit SARS-CoV-2 replication by 90% (IC90) of 6.9 μM. Furthermore, ΔQTc >60 milliseconds occurred after initiation of chloroquine treatment in 34% patients and during treatment QTc ≥500 milliseconds was observed in 46% of patients.ConclusionsRecommended dose chloroquine treatment results in plasma concentrations that are unlikely to inhibit viral replication. Furthermore, the incidence of QTc prolongation was high. The preclinical promise of chloroquine as antiviral treatment in patients with COVID-19 is overshadowed by its cardiac toxicity and lack of effective exposure. It is unlikely that a positive clinical effect will be found with chloroquine for treatment of COVID-19. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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