Hydroxychloroquine Concentrations Research Articles

Efficient removal of hydroxychloroquine sulfate using cocoa shell activated carbon: a green approach investigating equilibrium, kinetics, and thermodynamics

In recent years, the world has suffered from the pandemic of the century, known as COVID-19. A significant effort has been exerted to develop new and more efficient treatments in order to find an effective cure. As a result, various pharmaceutical products have been tested and utilized. However, the presence of emerging contaminants such as these pharmaceuticals in aquatic environments poses a serious threat, as their actual effects on both the environment and human health remain largely unknown. Therefore, the present study aims to investigate the potential use of activated carbon derived from cocoa shells for the effective removal of hydroxychloroquine (HCQ) from aqueous solutions. Batch experiments were conducted to evaluate the capability of this type of activated carbon to eliminate this persistent pharmaceutical from aqueous systems. The cocoa shell activated carbon demonstrated a high adsorption capacity (98%) under mild operating conditions, including an adsorption time of 180 min, a pH of 7, an activated carbon dosage of 1.5 g L−1, an initial HCQ concentration of 10 mg L−1, and a stirring speed of 400 rpm at 297 K. The adsorption kinetics were best described by the pseudo-second-order model, while intraparticle diffusion was found to be a suitable description for higher concentrations. Further insight was gained by applying isotherm and thermodynamic studies. The results indicated that the adsorption isotherm followed Langmuir, Freundlich, and Temkin models. Moreover, the thermodynamic analysis revealed that the adsorption of HCQ onto the cocoa shell-activated carbon is exothermic and spontaneous.

Genotype-guided new approach for dose optimisation of hydroxychloroquine administration in Chinese patients with SLE

ObjectivesThe study aims to investigate the impact of gene polymorphisms on blood hydroxychloroquine (HCQ) concentrations in patients with SLE and provide guidelines for individualised care.Methods489 Chinese patients with SLE taking...

Inhalable chitosan-based hydrogel as a mucosal adjuvant for hydroxychloroquine in the treatment for SARS-CoV-2 infection in a hamster model.

Effective therapy for COVID-19 remains limited. Hydroxychloroquine (HCQ) has been considered, but safety and efficacy concerns remain. Chitosan exhibits antiviral and immunomodulatory effects, yet how the combination of HCQ and chitosan performs in treating COVID-19 is unknown. Male Syrian hamsters were inoculated intranasally with standardized stocks of the SARS-CoV-2 virus. Hamsters were allocated to saline (PBS), chitosan oligosaccharide (COS), HCQ, or COS+HCQ groups and received corresponding drugs. On days 1, 7, and 14 post-infection, two animals from each group were euthanized for sample collection. Viral loads were measured in lung homogenates. Biochemistry markers, cytokines, and immunoglobulins were analyzed from hamster sera. HCQ concentrations were compared between the blood, bronchoalveolar lavage, and lung tissues. All groups underwent histopathology exams of the lungs. Additional hamsters were treated with the same drugs to assess for toxicities to the heart and liver. Among all groups, viral loads in the COS+HCQ group were the lowest by day 8. The COS+HCQ group produced the highest interleukin (IL)-6 levels on day 4, and the highest IL-10, IgA and IgG levels on day 8. HCQ concentrations were higher in the COS+HCQ group's lungs than the HCQ group, despite having received half the dose of HCQ. Histopathology demonstrated earlier inflammation resolution and swifter viral clearance in the COS+HCQ group. There was no evidence of cardiac or hepatic injury in hamsters that received HCQ. In hamsters infected with the SARS-CoV-2 virus, the combination of intranasal COS and HCQ was associated with increased HCQ absorption in the lungs, more effective immune responses, without increasing the risk of hepatic or cardiac injuries.

Analysis of Factors Influencing Whole Blood Hydroxychloroquine Concentration in Patients with Systemic Lupus Erythematosus in China.

The aim of this study was to determine the factors associated with the concentrations of hydroxychloroquine (HCQ) and its major metabolite, desethylhydroxychloroquine (DHCQ), in patients with systemic lupus erythematosus (SLE). Patients with SLE taking oral HCQ for at least 3months were recruited from the Department of Rheumatology and Immunology of Nanjing Drum Tower Hospital. Clinical characteristics and laboratory values were examined. The concentrations of HCQ and DHCQ were measured by high-performance liquid chromatography, and the effects of various factors on the concentrations were investigated. A total of 272 patients were included in this study. The average concentration of HCQ was 690.90ng/ml and the average concentration of DHCQ was 431.84ng/ml. Multivariate analysis indicated that gender (P = 0.015), age (year) (P < 0.001), weight (kg) (P = 0.013), duration of HCQ use (month) (P < 0.001), systemic lupus erythematosus disease activity index (SLEDAI) (P < 0.001), platelet count (× 109/l) (P < 0.001), immunoglobulin G levels (g/l) (P = 0.014) were associated with low HCQ concentrations. Gender (P = 0.006), duration of HCQ use (month) (P < 0.001), SLEDAI (P = 0.007), and platelet count (× 109/l) (P < 0.001) were associated with low DHCQ concentrations. Patients with SLE require long-term administration of HCQ, but blood levels vary widely between individuals. Studying the factors influencing the blood HCQ and DHCQ concentrations and optimizing the dose according to individual characteristics might help to improve the efficacy of HCQ. ChiCTR2300070628.

The Impact of Hydroxychloroquine on Primary Feto-Placental Endothelial Cells from Healthy and Early-Onset Preeclamptic Placentas.

Hydroxychloroquine (HCQ), an anti-malarial drug, is suggested as a promising candidate for the treatment of pregnancy-related disorders associated with endothelial activation, among which there is preeclampsia (PE). Arterial feto-placental endothelial cells (fpECAs) were isolated from control (CTR) and early-onset preeclamptic (EO-PE) placentas. The aim of this study was to test potential protective effects of HCQ in an in vitro model of endothelial activation as well as in cells isolated from EO-PE placentas. To mimic PE conditions, CTR fpECAs were exposed to a pro-inflammatory environment consisting of tumor necrosis factor α (TNF-α), interleukin (IL)-6 and IL-1β (furtherly referred as MIX) with or without varying concentrations of HCQ (1 µg/mL and 10 µg/mL). Their effect on wound healing and endothelial barrier integrity was analyzed. Variations in the expression of IL-8 and leukocyte adhesion molecules (LAM) on both mRNA and protein levels were determined between CTR and PE fpECAs in the presence or absence of HCQ. MIX decreased wound healing and stability of the endothelial barrier, but HCQ did not affect it. Significant differences between CTR and EO-PE fpECAs were observed in IL-8 mRNA, protein secretion, and vascular cell adhesion protein 1 (VCAM-1) mRNA expression levels. After challenging CTR fpECAs with MIX, upregulation of both mRNA and protein levels was observed in all molecules. Combined treatment of HCQ and MIX slightly lowered VCAM-1 total protein amount. In CTR fpECAs, treatment with low concentrations of HCQ alone (1 µg/mL) reduced basal levels of IL-8 and VCAM-1 mRNA and secretion of IL-8, while in EO-PE fpECAs, a higher (10µg/mL) HCQ concentration slightly reduced the gene expression of IL-8. Conclusion: These results provide additional support for the safety of HCQ, as it did not adversely affect endothelial functionality in control fpECAs at the tested concentration. Furthermore, the observed limited effects on IL-8 secretion in EO-PE fpECAs warrant further investigation, highlighting the need for clinical trials to assess the potential therapeutic effects of HCQ in preeclampsia. Conducting clinical trials would offer a more comprehensive understanding of HCQ's efficacy and safety, allowing us to explore its potential benefits and limitations in a real-world clinical setting.

Subtherapeutic hydroxychloroquine concentration is associated with increased disease activity and greater organ damage in lupus.

To investigate the effects of the serum HCQ concentration on clinical manifestations, disease activity and organ damage in a longitudinal cohort of SLE patients. The 338 SLE patients were assessed with respect to their demographic data, clinical and laboratory findings, Physician's Global Assessment (PGA), adjusted mean SLEDAI-2000 (AMS) and SLICC Damage Index (SDI) annually for 5 consecutive years. Patients were divided into two groups according to their serum HCQ concentration at baseline: subtherapeutic (<500 ng/ml) and therapeutic (≥500 ng/ml) groups. The impact of the HCQ concentration on the clinical outcomes was evaluated in a longitudinal analysis using a generalized estimating equation (GEE). Of the 338 patients, 287 (84.9%) were in the subtherapeutic group at baseline. This group had a higher incidence of newly developed LN (P = 0.036) and had been prescribed higher mean and cumulative doses of prednisolone (P = 0.003 and P = 0.013, respectively) than the therapeutic group. In multivariable analyses based on GEE, the subtherapeutic group had a higher AMS score (β = 1.398, 95% CI 0.607, 2.189; P < 0.001), higher PGA score (β = 0.328, 95% CI 0.215, 0.441; P < 0.001) and higher SDI score (β = 0.366, 95% CI 0.061, 0.671; P = 0.019) across all 5 years. The subtherapeutic HCQ concentration was associated with the development of new-onset LN, and had significant associations with disease activity and cumulative organ damage in SLE patients over time.

A linked physiologically based pharmacokinetic model for hydroxychloroquine and metabolite desethylhydroxychloroquine in SARS-CoV-2(-)/(+) populations.

Hydroxychloroquine (HCQ) is Food and Drug Administration (FDA)-approved for malaria, systemic and chronic discoid lupus erythematosus, and rheumatoid arthritis. Because HCQ has a proposed multimodal mechanism of action and a well-established safety profile, it is often investigated as a repurposed therapeutic for a range of indications. There is a large degree of uncertainty in HCQ pharmacokinetic (PK) parameters which complicates dose selection when investigating its use in new disease states. Complications with HCQ dose selection emerged as multiple clinical trials investigated HCQ as a potential therapeutic in the early stages of the COVID-19 pandemic. In addition to uncertainty in baseline HCQ PK parameters, it was not clear if disease-related consequences of SARS-CoV-2 infection/COVID-19 would be expected to impact the PK of HCQ and its primary metabolite desethylhydroxychloroquine (DHCQ). To address the question whether SARS-CoV-2 infection/COVID-19 impacted HCQ and DHCQ PK, dried blood spot samples were collected from SARS-CoV-2(-)/(+) participants administered HCQ. When a previously published physiologically based pharmacokinetic (PBPK) model was used to fit the data, the variability in exposure of HCQ and DHCQ was not adequately captured and DHCQ concentrations were overestimated. Improvements to the previous PBPK model were made by incorporating the known range of blood to plasma concentration ratios (B/P) for each compound, adjusting HCQ and DHCQ distribution settings, and optimizing DHCQ clearance. The final PBPK model adequately captured the HCQ and DHCQ concentrations observed in SARS-CoV-2(-)/(+)participants, and incorporating COVID-19-associated changes in cytochrome P450 activity did not further improve model performance for the SARS-CoV-2(+) population.

Low estimated glomerular filtration rate is an independent risk factor for higher hydroxychloroquine concentration

BackgroundThe aim of this study was to analyze the relationship of the estimated glomerular filtration rate (eGFR) to hydroxychloroquine (HCQ) blood concentrations in systemic lupus erythematosus (SLE) patients.MethodPatients with SLE who had been taking HCQ for more than 12 months were recruited. All subjects gave written informed consent. Various clinical characteristics and laboratory values were examined. The blood concentration of HCQ was measured by high-performance liquid chromatography, and the relationship of eGFR to HCQ blood concentration was mainly investigated.ResultIn total, 115 patients with SLE receiving long-term HCQ therapy were included in the study. The median concentration of HCQ was 1096 ng/ml (range 116–8240 ng/ml). The eGFR was strongly associated with blood concentration of HCQ (P = 0.011, P < 0.05), when adjusted for age, sex, body mass index (BMI), weight-adjusted dose, prednisone use and immunosuppressive drug use. No statistically significant association were found between age, duration, BMI, weight-adjusted HCQ dose, corticosteroid use, immunosuppressant use and blood concentrations of HCQ.ConclusionWe provided novel evidence that impaired renal function influenced the blood concentration of HCQ. Patients with low eGFR need to adjust the HCQ dosage according to the monitoring results of HCQ blood concentrations.Key points• A higher HCQ blood concentration was associated with low eGFR.• This finding reinforces the importance of routine HCQ measurement to maintain normal blood concentrations.• HCQ blood monitoring will be useful for dose modification in patients with renal dysfunction.

Immunosuppression by hydroxychloroquine: mechanistic proof in in vitro experiments but limited systemic activity in a randomized placebo-controlled clinical pharmacology study

Based on its wide range of immunosuppressive properties, hydroxychloroquine (HCQ) is used for the treatment of several autoimmune diseases. Limited literature is available on the relationship between HCQ concentration and its immunosuppressive effect. To gain insight in this relationship, we performed in vitro experiments in human PBMCs and explored the effect of HCQ on T and B cell proliferation and Toll-like receptor (TLR)3/TLR7/TLR9/RIG-I-induced cytokine production. In a placebo-controlled clinical study, these same endpoints were evaluated in healthy volunteers that were treated with a cumulative dose of 2400 mg HCQ over 5 days. In vitro, HCQ inhibited TLR responses with IC50s > 100 ng/mL and reaching 100% inhibition. In the clinical study, maximal HCQ plasma concentrations ranged from 75 to 200 ng/mL. No ex vivo HCQ effects were found on RIG-I-mediated cytokine release, but there was significant suppression of TLR7 responses and mild suppression of TLR3 and TLR9 responses. Moreover, HCQ treatment did not affect B cell and T cell proliferation. These investigations show that HCQ has clear immunosuppressive effects on human PBMCs, but the effective concentrations exceed the circulating HCQ concentrations under conventional clinical use. Of note, based on HCQ’s physicochemical properties, tissue drug concentrations may be higher, potentially resulting in significant local immunosuppression. This trial is registered in the International Clinical Trials Registry Platform (ICTRP) under study number NL8726.

κ-Carrageenan/Sodium Alginate: A New Synthesis Route and Rapid Adsorbent for Hydroxychloroquine Drug

In recent years, the huge amounts of chemicals that are used as drugs and their derivatives have been exposed to the environment due to the COVID-19 pandemic. Some of these drugs (i.e. hydroxychloroquine (HCQ)) have a serious risk on aquatic media. In this study, carrageenan/sodium alginate (κC/Sa) was investigated as a biopolymer, environmentally friendly, and rapidly adsorbent to eliminate HCQ from its aqueous solution. The biopolymer (κC/Sa) was synthesized by free radical polymerization assisted by ultrasound in the presence of acrylic acid as cross-linkage and potassium persulfate as an initiator. The natural κC/Sa was characterized by FTIR, XRD, BET, BJH, and SEM techniques. The produced co-polymer had a mesoporous surface with high purity and significant thermal stability. The best parameters were determined to be 0.05 g biopolymer, 200 ppm initial HCQ concentration, salts, and pH = 7. The adsorption mechanism follows a pseudo second-order kinetic model, and the adsorption isotherm follows a Freundlich model, with qe reaching 89.8 mg/g at 500 ppm HCQ. Thermodynamic studies indicated that the adsorption of hydroxychloroquine drugs was an exothermic spontaneous process.

Effects of hydroxychloroquine on atrial electrophysiology in in silico wild-type and PITX2+/- atrial cardiomyocytes.

Hydroxychloroquine (HCQ) is commonly used in the treatment of autoimmune diseases and increases the risk of QT interval prolongation. However, it is unclear how HCQ affects atrial electrophysiology and the risk of atrial fibrillation (AF). We quantitatively examined the potential atrial arrhythmogenic effects of HCQ on AF using acomputational model of human atrial cardiomyocytes. We measured atrial electrophysiological markers after systematically varying HCQ concentrations. The HCQ concentrations were positively correlated with the action potential duration (APD), resting membrane potential, refractory period, APD alternans threshold, and calcium transient alternans threshold (p < 0.05). By contrast, HCQ concentrations were inversely correlated with the maximum upstroke velocity and calcium transient amplitude (p < 0.05). When the therapeutic concentration (Cmax) of HCQ was applied, HCQ increased APD90 by 1.4% in normal sinus rhythm, 1.8% in wild-type AF, and 2.6% in paired-like homeodomain transcription factor2 (PITX2)+/- AF, but did not affect the alternans thresholds. The overall in silico results suggest no significant atrial arrhythmogenic effects of HCQ at Cmax, instead implying apotential antiarrhythmic role of low-dose HCQ in AF. However, at an HCQ concentration of fourfold Cmax, arapid pacing rate of 4 Hz induced prominent APD alternans, particularly in the PITX2+/- AF model. Our in silico analysis suggests a potential antiarrhythmic role of low-dose HCQ in AF. Concomitant PITX2 mutations and high-dose HCQ treatments may increase the risk of AF, and this potential genotype/dose-dependent arrhythmogenic effect of HCQ should be investigated further.

Pharmacokinetics of hydroxychloroquine in paediatric lupus: data from a novel, direct-to-family clinical trial

ObjectiveDetermine the pharmacokinetics (PK) and exposure–response of hydroxychloroquine (HCQ) and desethylhydroxychloroquine (DHCQ) in paediatric SLE (pSLE).MethodsWe conducted an exploratory phase 2, direct-to-family trial. Children enrolled in the Childhood Arthritis and...

Comparison of Hydroxychloroquine Concentration Among Whole Blood, Serum, and Plasma Samples in Indian Patients With Lupus Nephritis

Comparison of Hydroxychloroquine Concentration Among Whole Blood, Serum, and Plasma Samples in Indian Patients With Lupus Nephritis

Synthesis of Reduced Graphene Oxide by Ethyl Acetate and Its Utilization in Determining Hydroxychloroquine in Wastewater and Pharmaceutical Samples

AbstractAn easy and sensitive sensor made by carbon paste modified with reduced graphene oxide rGO‐CPE was developed for the detection of hydroxychloroquine (HCQ). Graphene oxide GO was reduced using ethyl acetate. Scanning electron microscope and X‐ray diffraction (XRD) were used for the characterization of rGO powder. The reduction of graphene oxide was confirmed by the disappearance of the identical peak of graphite in the XRD pattern. Herein, the modified electrode rGO‐CPE showed stronger electrochemical activity compared to bare CPE. The electrochemical behavior of HCQ was studied by cyclic voltammetry, electrochemical impedance spectroscopy, and chronoamperometry. The mechanism of the HCQ oxidation in the surface of rGO‐CPE was found to be controlled by an adsorption process with the transfer of 2 electrons. Furthermore, the standard heterogeneous rate constant (Ks) and the surface concentration of electroactive species (Γ) were calculated and the obtained values are 1.03×10−2 cm s−1 and 1.07×10−10 mol cm−2, respectively. Differential pulse voltammetry was used for HCQ quantification as a result a linear relationship between HCQ concentration and the oxidation peak current was obtained in the range from 1.0×10−7 to 8.0×10−6 mol L−1 and from 8.0×10−6 to 1.0×10−4 mol L−1, with a detection limit (LOD) of 6.29×10−8 mol L−1 and a sensitivity of 6.42 A L mol−1 cm−2. Moreover, the rGO‐CPE was successfully applied for the detection of HCQ in wastewater and pharmaceutical samples.

Pharmacokinetics of hydroxychloroquine in Japanese systemic lupus erythematosus patients with renal impairment.

Reduction of the hydroxychloroquine (HCQ) dosage is recommended in systemic lupus erythematosus (SLE) patients with renal impairment, but a pharmacokinetics (PK) study of patients with renal impairment has not yet been performed. We investigated the PK of both single and multiple doses of HCQ and its metabolites in SLE patients with renal impairment who newly started HCQ at a daily dose of 300 mg based on an ideal body weight dosage of 6.5 mg/kg. Population PK analysis was performed using a non-linear mixed-effects model. In total, 219 samples from 21 patients were analysed. The PK of HCQ in blood after single and multiple oral administrations followed the two-compartment model. At steady state, the concentration ratio of HCQ to each metabolite was HCQ:desethylhydroxychloroquine:desethylchloroquine:bisdesethylchloroquine = 1:0.28:0.1:0.06. The HCQ concentration correlated positively with that of each metabolite. The estimated values (relative standard error) of the population PK parameters were the total clearance at 110 l/h (31%) and a central volume of distribution of 398 l (19%). Co-administration of prednisolone and age, but not renal impairment, were factors affecting the total clearance of HCQ. From the PK perspective, a dosage reduction is unnecessary in SLE patients with impaired renal function.

Removal of hydroxychloroquine from an aqueous solution using living microalgae: Effect of operating parameters on removal efficiency and mechanisms.

Wastewater contaminated with hydroxychloroquine (HCQ) poses a serious threat to the environment and human life. This study aimed to evaluate the ability of living microalgae to remove HCQ from an aqueous solution. Batch mode experiments were conducted under different conditions to investigate the effect of operating parameters on HCQ removal efficiency and mechanisms. Equilibrium, kinetic and thermodynamic study was also carried out to better describe the interactions between HCQ and microalgae. The maximum HCQ removal was 92.10 ± 1.25% obtained under optimal pH of 9.9 ± 0.1, a contact time of 45 min, a stirring speed of 300 rpm, an initial HCQ concentration of 20 mg/L, and a microalgae dose of 100 mg/L. The Langmuir isotherm and the pseudo-second-order kinetic model were best suited for the biosorption experiments, and the maximum biosorption capacity was 339.02 mg/g. The thermodynamic study showed that the biosorption process was exothermic and spontaneous. Experiments on real wastewater showed that the HCQ removal was not significantly affected by the presence of other contaminants in the water. PRACTITIONER POINTS: The best HCQ removal was 92.10 ± 1.25% obtained under optimal conditions. The Langmuir isotherm and the pseudo-second-order kinetic model were best suited for the biosorption experiments. The maximum biosorption capacity was 339.02 mg/g. The thermodynamic study showed that the biosorption process was exothermic and spontaneous. The microalgae studied can be successfully used in HCQ removal from water.

Population Pharmacokinetics of Hydroxychloroquine Sulfate in Healthcare Workers, Given for Prophylaxis Against Coronavirus Disease 2019 (COVID-19) in India.

Healthcare workers (HCWs) and frontline workers were recommended hydroxychloroquine (HCQ) 400 mg twice a day on day 1, followed by 400 mg once weekly for the next 7 weeks, as prophylaxis against COVID‐19. There was limited information on the population pharmacokinetics (popPK) of HCQ in an Indian setting when administered for prophylaxis against COVID‐19, and hence this study was proposed. It was a multicentric prospective study conducted at 3 sites in India wherein HCWs who were already on HCQ prophylaxis, who were about to start prophylaxis or who had stopped the prophylaxis for any reason were enrolled. Each participant gave 2 to 6 blood samples at different time points and whole‐blood HCQ concentrations were assayed using liquid chromatography with tandem mass spectrometry (LC MS/MS). popPK analysis was performed using PUMAS 1.1.0. A total of N = 338 blood samples from N = 121 participants were included in the popPK analysis. A 2‐compartment structural model with linear elimination was able to explain the observed data. Body weight was found to be a significant covariate influencing drug clearance. The final model was assessed using goodness‐of‐fit plots, a visual predictive check and a bootstrap, all of which confirmed that the model was appropriate. Simulations based on the current regimen showed that trough values were below the half‐maximal effective concentration (EC50) of 0.7 μmol against COVID‐19. A new weight‐based dosage regimen was proposed to maintain the trough concentration above the EC50 threshold.

The relationship between hydroxychloroquine plasma concentration and COVID-19 outcomes in rheumatoid arthritis patients in Saudi Arabia

BackgroundThe drug hydroxychloroquine (HCQ) is widely used to treat rheumatoid arthritis (RA) and has been repurposed for the treatment of COVID-19. This study aims to determine whether HCQ concentration levels in individuals with RA alter the incidence of COVID-19 or its complications. MethodsWe collected plasma samples from 13 individuals with confirmed rheumatoid arthritis (RA) to measure HCQ concentration levels. The study included individuals at least 18 years old who had been taking HCQ for at least six months at daily doses ranging from 200 to 400 mg. ResultsThe study enrolled a total of 13 RA patients. All patients were chronic HCQ users. Among the 13 patients, 7 patients were receiving HCQ at a dose of 200 mg per day, and 6 patients were receiving HCQ at a dose of 400 mg per day. COVID-19 confirmed cases accounted for approximately 46% of all patients. Half of the infected patients (n = 3) were taking a daily dose of 200 mg daily, while the other half were taking 400 mg daily. COVID-19 symptoms ranged from mild to moderate, and the intensity of the symptoms was not severe enough to necessitate hospitalization. COVID-19 symptoms in RA patients included headache, fever, fatigue, dry cough, and loss of taste or smell. ConclusionsOur findings indicated that there was no correlation between HCQ concentrations in rheumatoid arthritis patients and the occurrence of COVID-19 or its complications.

Hydroxychloroquine Blood Concentrations Can Be Clinically Relevant Also After Drug Discontinuation.

Background and ObjectiveHydroxychloroquine 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.MethodsWe 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.ResultsOur 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.ConclusionsThe 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.

Hydroxychloroquine concentrations persist after drug discontinuation

Hydroxychloroquine concentrations persist after drug discontinuation