Concentration-dependent mortality of chloroquine in overdose
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...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
eLife Sciences Publications
2020
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| _version_ | 1797095097285738496 |
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| author | Watson, JA Tarning, J Hoglund, RM Baud, FJ Megarbane, B Clemessy, J-L White, NJ |
| author_facet | Watson, JA Tarning, J Hoglund, RM Baud, FJ Megarbane, B Clemessy, J-L White, NJ |
| author_sort | Watson, JA |
| collection | OXFORD |
| description | 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 umol/L (95% credible interval 10.1-17.7) were associated with 1% mortality. Prolongation of ventricular depolarisation is concentration-dependent with a QRS duration >150 msec independently highly predictive of mortality in chloroquine self-poisoning. Pharmacokinetic modelling predicts that most high dose regimens trialled in COVID-19 are unlikely to cause serious cardiovascular toxicity. |
| first_indexed | 2024-03-07T04:23:11Z |
| format | Journal article |
| id | oxford-uuid:cbb82bc9-d327-4a1e-880f-192cf4c46a5c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:23:11Z |
| publishDate | 2020 |
| publisher | eLife Sciences Publications |
| record_format | dspace |
| spelling | oxford-uuid:cbb82bc9-d327-4a1e-880f-192cf4c46a5c2022-03-27T07:16:58ZConcentration-dependent mortality of chloroquine in overdoseJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:cbb82bc9-d327-4a1e-880f-192cf4c46a5cEnglishSymplectic ElementseLife Sciences Publications2020Watson, JATarning, JHoglund, RMBaud, FJMegarbane, BClemessy, J-LWhite, NJHydroxychloroquine 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 umol/L (95% credible interval 10.1-17.7) were associated with 1% mortality. Prolongation of ventricular depolarisation is concentration-dependent with a QRS duration >150 msec independently highly predictive of mortality in chloroquine self-poisoning. Pharmacokinetic modelling predicts that most high dose regimens trialled in COVID-19 are unlikely to cause serious cardiovascular toxicity. |
| spellingShingle | Watson, JA Tarning, J Hoglund, RM Baud, FJ Megarbane, B Clemessy, J-L White, NJ Concentration-dependent mortality of chloroquine in overdose |
| title | Concentration-dependent mortality of chloroquine in overdose |
| title_full | Concentration-dependent mortality of chloroquine in overdose |
| title_fullStr | Concentration-dependent mortality of chloroquine in overdose |
| title_full_unstemmed | Concentration-dependent mortality of chloroquine in overdose |
| title_short | Concentration-dependent mortality of chloroquine in overdose |
| title_sort | concentration dependent mortality of chloroquine in overdose |
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