Abstract: Communication Drug Repositioning in Intensive Care Patients and Pharmacokinetic Variability: The Illustration of Hydroxychloroquine Gwendoline Ragonnet 1, *, Elisabeth Jouve 1 , Lionel Velly 2 , Marc Leone 3 , Gary Duclos 3 , Jeremy Bourenne 4 , Karim Harti Souab 5 , Caroline Solas 6 and Romain Guilhaumou 1 1 2 3 4 5 6 *



 Citation: Ragonnet, G.; Jouve, E.; Velly, L.; Leone, M.; Duclos, G.; Bourenne, J.; Harti Souab, K.; Solas, C.; Guilhaumou, R. Drug Repositioning in Intensive Care Patients and Pharmacokinetic Variability: The Illustration of Hydroxychloroquine. Future Pharm. 2022, 2, 92–98. https://doi.org/ 10.3390/futurepharmacol2010007 Academic Editor: Fabrizio Schifano Received: 7 February 2022 Accepted: 14 March 2022 Published: 19 March 2022 Publisher’s Note: MDPI stays neutral Service de Pharmacologie Clinique et Pharmacovigilance, Institut des Neurosciences des Systèmes, Inserm UMR 11600, Aix Marseille University APHM, CEDEX 5, 13385 Marseille, France; elisabeth.jouve@ap-hm.fr (E.J.); romain.guilhaumou@ap-hm.fr (R.G.) Department of Anesthesiology and Critical Care Medicine, Timone University Hospital, Aix Marseille University APHM, 13005 Marseille, France; lionel.velly@ap-hm.fr Department of Anesthesiology and Intensive Care, Timone University Hospital, Aix Marseille University APHM, 13015 Marseille, France; marc.leone@ap-hm.fr (M.L.); gary.duclos@ap-hm.fr (G.D.) Emergency Resuscitation Department, Timone University Hospital, Aix Marseille University APHM, CEDEX 5, 13385 Marseille, France; jeremy.bourenne@ap-hm.fr Intensive Care Unit, Timone University Hospital, Aix Marseille University APHM, CEDEX 5, 13385 Marseille, France; karim.harti-souab@ap-hm.fr Unité des Virus Émergents IRD190, Inserm 1207, Laboratoire de Pharmacocinétique et Toxicologie, CEDEX 5, 13385 Marseille, France; caroline.solas@ap-hm.fr Correspondence: gwendoline.ragonnet@ap-hm.fr Abstract: During the SARS-CoV-2 pandemic, hydroxychloroquine (HCQ), was among the first drugs to be tested due to demonstrated in vitro antiviral activity against SARS-CoV-2. Pharmacokinetic variability was expected due to the frequent comorbidities and pathophysiological modifications observed in severe COVID-19 patients hospitalized in intensive care units (ICUs). The aim of this study was to describe HCQ plasmatic concentrations in ICUs and assess variability factors. A multicentric retrospective study was carried in four ICUs in Marseille from March to April 2020. There were two dosing regimens: 400 mg after a 400 mg loading dose (DR1); and 600 mg without a loading dose (DR2). HCQ concentrations were determined every 2 or 3 days. The impacts of demo-graphic, biological, and clinical covariates were investigated. The median HCQ concentration was: 0.096 mg/L on day (D) 2, 0.129 mg/L on D3 to D5, 0.140 mg/L on D6 to D10 for DR1 versus 0.116 mg/L, 0.261 mg/L, and 0.30 mg/L, respectively, for DR2. At D2, 53.9% and 46.2% of patients with DR1 and DR2, respectively, presented HCQP concentrations <0.1 µg/mL and 48.2% versus 10.7% at D3 to D5. Time post-initiation, dosing regimen, nasogastric administration, and weight showed significant association with HCQ variability. The high proportion of suboptimal HCQ concentrations can be explained by a lack of optimized dosing regimen and numerous pathophysiological changes in the COVID-19/ICU population. with regard to jurisdictional claims in published maps and institutional affil- Keywords: hydroxychloroquine;..