Background and Objective

Hydroxychloroquine was widely used during the severe acute respiratory syndrome coronavirus 2 pandemic as an antiviral drug. Most previous pharmacokinetic/pharmacodynamic studies on hydroxychloroquine were conducted on healthy volunteers or patients receiving long-term therapy. There are no studies on the elimination of hydroxychloroquine after short-term treatments. Hydroxychloroquine is known to have a pro-arrhythmic effect through QT interval prolongation, but data in this setting are not conclusive. Our aims were to estimate the time needed for hydroxychloroquine concentrations (C_HCQ) to drop to a safe concentration (500 ng/mL) after a short-term therapeutic cycle and to correlate the corrected QT interval with C_HCQ.

Methods

We collected blood samples and electrocardiograms of patients who underwent short-term therapy with hydroxychloroquine during drug intake and after discontinuation. Hydroxychloroquine concentrations were determined by high-performance liquid chromatography–tandem mass spectrometry and analysed with a linear regression model to estimate the elimination time of the drug after its discontinuation. We conducted a multivariate analysis of the corrected QT interval correlation with C_HCQ.

Results

Our data suggest that short-term hydroxychloroquine courses can generate significant C_HCQ persisting above 500 ng/mL up to 16 days after discontinuation of treatment. Corrected QT interval prolongation significantly correlates with C_HCQ.

Conclusions

The study confirms the long half-life of hydroxychloroquine and its effect on the corrected QT interval even after short-term courses of the drug. This can inform the clinician using hydroxychloroquine treatments that it would be safer to start or re-initiate treatments with corrected QT interval-prolonging potential 16 days after hydroxychloroquine discontinuation.

中文翻译：

---

停药后羟氯喹的血液浓度也可能具有临床相关性

背景和目的

羟氯喹在严重急性呼吸综合征冠状病毒2大流行期间被广泛用作抗病毒药物。此前大多数关于羟氯喹的药代动力学/药效学研究都是在健康志愿者或接受长期治疗的患者身上进行的。目前还没有关于短期治疗后消除羟氯喹的研究。已知羟氯喹通过延长 QT 间期而具有促心律失常作用，但该情况下的数据尚不明确。我们的目的是估计短期治疗周期后羟氯喹浓度 ( C _{HCQ ) 降至安全浓度 (500 ng/mL) 所需的时间，并将校正的 QT 间期与}C _HCQ相关联。

方法

我们收集了接受羟氯喹短期治疗的患者在服药期间和停药后的血液样本和心电图。通过高效液相色谱-串联质谱法测定羟氯喹浓度，并使用线性回归模型进行分析，以估计停药后药物的消除时间。我们对校正后的 QT 间期与C _HCQ的相关性进行了多变量分析。

结果

我们的数据表明，短期羟氯喹疗程可产生显着的C _HCQ，在停止治疗后 16 天内持续高于 500 ng/mL。校正的 QT 间期延长与C _HCQ显着相关。

结论

该研究证实了羟氯喹的长半衰期及其对校正 QT 间期的影响，即使在短期用药后也是如此。这可以告知使用羟氯喹治疗的临床医生，在羟氯喹停药 16 天后开始或重新开始具有校正 QT 间期延长潜力的治疗会更安全。