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.

中文翻译：

---

氯喹过量时的浓度依赖性死亡率


羟氯喹和氯喹广泛用于治疗疟疾和风湿病，现在也用于预防和治疗 COVID-19。虽然通常是安全的，但过量服用可能会致命。体外数据表明，感染 COVID-19 需要高浓度和高剂量，但目前尚无令人信服的临床疗效证据。贝叶斯回归模型拟合了 302 名有意服用过量氯喹的前瞻性研究法国患者（其中 33 人死亡（11%））和 16 名服用 620 毫克基础氯喹单剂量的健康志愿者的生存结果和心电图 QRS 持续时间。全血浓度为 13.5 µmol/L（95% 可信区间 10.1–17.7）与 1% 死亡率相关。心室除极的延长具有浓度依赖性，QRS 持续时间 >150 毫秒，可以独立地高度预测氯喹自中毒的死亡率。药代动力学模型预测，在 COVID-19 中试验的大多数高剂量方案不太可能引起严重的心血管毒性。