Drug Repositioning in Intensive Care Patients and Pharmacokinetic Variability: The Illustration of Hydroxychloroquine
Ragonnet et al.,
Drug Repositioning in Intensive Care Patients and Pharmacokinetic Variability: The Illustration of..,
Future Pharmacology, doi:10.3390/futurepharmacol2010007 (Dosing)
Comparison of two HCQ dosing regimens, showing high inter-individual variability of HCQ concentrations (as in
[Ruiz]), and significantly better plasma concentrations for the dosing regimen including a loading dose.
Ragonnet et al., 19 Mar 2022, peer-reviewed, 9 authors.
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.
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Keywords: hydroxychloroquine;..
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