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. 2022 Jun;22(2):155-163.
doi: 10.1007/s40268-022-00387-2. Epub 2022 May 13.

Hydroxychloroquine Blood Concentrations Can Be Clinically Relevant Also After Drug Discontinuation

Simona De Gregori  1 , Francesco Falaschi  2 , Alessia Ballesio  3 , Alessandra Fusco  3 , Elisa Cremonte  3 , Roberta Canta  3 , Umberto Sabatini  3 , Mariadelfina Molinaro  1 , Carlo Soffiantini  3 , Alba Nardone  3 , Alessandro Vicentini  4 , Annalisa De Silvestri  5 , Antonio Di Sabatino  6
Affiliations

Hydroxychloroquine Blood Concentrations Can Be Clinically Relevant Also After Drug Discontinuation

Simona De Gregori et al. Drugs R D. 2022 Jun.

Abstract

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 (CHCQ) to drop to a safe concentration (500 ng/mL) after a short-term therapeutic cycle and to correlate the corrected QT interval with CHCQ.

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 CHCQ.

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

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.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Fig. 1
Fig. 1
Representative chromatogram of the analyte and ion spray. a Hydroxychloroquine (HCQ), m/z 336.1 → 179.04 and 247.03 and b hydroxychloroquine-D4 (HCQ-D4), m/z 340.1 → 251.03. Collision energies (CE, eV) are reported on the right side of the peaks
Fig. 2
Fig. 2
Regression model curve of a normalised hydroxychloroquine whole blood concentration (nCHCQ) for a total dose taken of 4000 mg; the horizontal line represents the concentration of 500 ng/mL considered as a safety threshold; the upper 95% confidence interval (CI) of the model intercepts the line at 16 days from hydroxychloroquine treatment cessation. nCHCQ HCQ whole blood concentrations normalised for a total dose taken of 4000 mg
See this image and copyright information in PMC

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