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Concentration-dependent mortality of chloroquine in overdose.
Elife. 2020 07 08; 9E

Abstract

Hydroxychloroquine and chloroquine are used extensively in malaria and rheumatological conditions, and now in COVID-19 prevention and treatment. Although generally safe they are potentially lethal in overdose. In-vitro data suggest that high concentrations and thus high doses are needed for COVID-19 infections, but as yet there is no convincing evidence of clinical efficacy. Bayesian regression models were fitted to survival outcomes and electrocardiograph QRS durations from 302 prospectively studied French patients who had taken intentional chloroquine overdoses, of whom 33 died (11%), and 16 healthy volunteers who took 620 mg base chloroquine single doses. Whole blood concentrations of 13.5 µmol/L (95% credible interval 10.1-17.7) were associated with 1% mortality. Prolongation of ventricular depolarization is concentration-dependent with a QRS duration >150 msec independently highly predictive of mortality in chloroquine self-poisoning. Pharmacokinetic modeling predicts that most high dose regimens trialled in COVID-19 are unlikely to cause serious cardiovascular toxicity.

Authors+Show Affiliations

Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.Assistance Publique - Hôpitaux de Paris, Paris, France. Université de Paris, Paris, France.Université de Paris, INSERM UMRS-11 44, Paris, France. Reanimation Medicale et Toxicologique, Hopital Lariboisiere, Paris, France.Assistance Publique - Hôpitaux de Paris, Paris, France. Reanimation Medicale et Toxicologique, Hopital Lariboisiere, Paris, France. Clinique du Sport, Paris, France.Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32639233

Citation

Watson, James A., et al. "Concentration-dependent Mortality of Chloroquine in Overdose." ELife, vol. 9, 2020.
Watson JA, Tarning J, Hoglund RM, et al. Concentration-dependent mortality of chloroquine in overdose. Elife. 2020;9.
Watson, J. A., Tarning, J., Hoglund, R. M., Baud, F. J., Megarbane, B., Clemessy, J. L., & White, N. J. (2020). Concentration-dependent mortality of chloroquine in overdose. ELife, 9. https://doi.org/10.7554/eLife.58631
Watson JA, et al. Concentration-dependent Mortality of Chloroquine in Overdose. Elife. 2020 07 8;9 PubMed PMID: 32639233.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Concentration-dependent mortality of chloroquine in overdose. AU - Watson,James A, AU - Tarning,Joel, AU - Hoglund,Richard M, AU - Baud,Frederic J, AU - Megarbane,Bruno, AU - Clemessy,Jean-Luc, AU - White,Nicholas J, Y1 - 2020/07/08/ PY - 2020/05/06/received PY - 2020/07/07/accepted PY - 2020/7/9/pubmed PY - 2020/8/22/medline PY - 2020/7/9/entrez KW - bayesian KW - chloroquine KW - human KW - human biology KW - medicine KW - overdose KW - pharmacodynamics KW - pharmacokinetics JF - eLife JO - Elife VL - 9 N2 - Hydroxychloroquine and chloroquine are used extensively in malaria and rheumatological conditions, and now in COVID-19 prevention and treatment. Although generally safe they are potentially lethal in overdose. In-vitro data suggest that high concentrations and thus high doses are needed for COVID-19 infections, but as yet there is no convincing evidence of clinical efficacy. Bayesian regression models were fitted to survival outcomes and electrocardiograph QRS durations from 302 prospectively studied French patients who had taken intentional chloroquine overdoses, of whom 33 died (11%), and 16 healthy volunteers who took 620 mg base chloroquine single doses. Whole blood concentrations of 13.5 µmol/L (95% credible interval 10.1-17.7) were associated with 1% mortality. Prolongation of ventricular depolarization is concentration-dependent with a QRS duration >150 msec independently highly predictive of mortality in chloroquine self-poisoning. Pharmacokinetic modeling predicts that most high dose regimens trialled in COVID-19 are unlikely to cause serious cardiovascular toxicity. SN - 2050-084X UR - https://www.unboundmedicine.com/medline/citation/32639233/Concentration_dependent_mortality_of_chloroquine_in_overdose_ L2 - https://doi.org/10.7554/eLife.58631 DB - PRIME DP - Unbound Medicine ER -