Chloroquine for treatment of COVID-19 - a pig in a poke?

Bruggemann, R. J. M.; Moes, D. J. A. R.; van Rhee, K. p.; van 't Veer, N. E.; Koch, B. C. P.; van Rossum, M.; Vermeulen Windsant, A.; Reijers, M. H. E.; van Kimmenade, R. R. J.; Rahamat-Langedoen, J.; Rettig, T. C. D.; van Raalte, R.; van Paassen, J.; Polderman, F.; van der Linden, P. D.; Frenzel, T.; de Mast, Q.; Burger, D. M.; Schouten, J.; van de Veerdonk, F.; Pickkers, P.; ter Heine, R.

Objective: Chloroquine 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. Design: A prospective observational study. Setting: Dutch hospitals Patients: Patients admitted to the hospital for treatment of COVID-19. Interventions: Pharmacokinetic sampling Measurements: The plasma concentrations of chloroquine and desethylchloroquine and QTc time. Main Results: A total of 83 patients were included. The median (IQR) plasma concentration chloroquine during treatment was 1.05 mol/L (0.63 - 1.55 mol/L). None of the patients reached exposure exceeding the concentration to inhibit SARS-CoV-2 replication by 90% (IC90) of 6.9 M. Furthermore, {Delta}QTc >60 milliseconds occurred after initiation of chloroquine treatment in 34% patients and during treatment QTc [≥]500 milliseconds was observed in 46% of patients. Conclusions: Recommended 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.