Pharmacokinetics and pharmacodynamics of hydroxychloroquine in hospitalized patients with COVID-19.
Identifieur interne : 000363 ( Main/Corpus ); précédent : 000362; suivant : 000364Pharmacokinetics and pharmacodynamics of hydroxychloroquine in hospitalized patients with COVID-19.
Auteurs : Noël Zahr ; Saik Urien ; Benoit Llopis ; Valérie Pourcher ; Olivier Paccoud ; Alexandre Bleibtreu ; Julien Mayaux ; Estelle Gandjbakhch ; Guillaume Hekimian ; Alain Combes ; Olivier Benveniste ; David Saadoun ; Yves Allenbach ; Bruno Pinna ; Patrice Cacoub ; Christian Funck-Brentano ; Joe-Elie SalemSource :
- Therapie [ 1958-5578 ] ; 2021.
Abstract
BACKGROUND
Hydroxychloroquine (HCQ) dosage required to reach circulating levels that inhibit SARS-Cov-2 are extrapolated from pharmacokinetic data in non-COVID-19 patients.
METHODS
We performed a population-pharmacokinetic analysis from 104 consecutive COVID-19 hospitalized patients (31 in intensive care units, 73 in medical wards, n=149 samples). Plasma HCQ concentration were measured using high performance liquid chromatography with fluorometric detection. Modelling used Monolix-2019R2.
RESULTS
HCQ doses ranged from 200 to 800mg/day administered for 1 to 11days and median HCQ plasma concentration was 151ng/mL. Among the tested covariates, only bodyweight influenced elimination oral clearance (CL) and apparent volume of distribution (Vd). CL/F (F for unknown bioavailability) and Vd/F (relative standard-error, %) estimates were 45.9L/h (21.2) and 6690L (16.1). The derived elimination half-life (t1/2) was 102h. These parameters in COVID-19 differed from those reported in patients with lupus, where CL/F, Vd/F and t1/2 are reported to be 68L/h, 2440 L and 19.5h, respectively. Within 72h of HCQ initiation, only 16/104 (15.4%) COVID-19 patients had HCQ plasma levels above the in vitro half maximal effective concentration of HCQ against SARS-CoV-2 (240ng/mL). HCQ did not influence inflammation status (assessed by C-reactive protein) or SARS-CoV-2 viral clearance (assessed by real-time reverse transcription-PCR nasopharyngeal swabs).
CONCLUSION
The interindividual variability of HCQ pharmacokinetic parameters in severe COVID-19 patients was important and differed from that previously reported in non-COVID-19 patients. Loading doses of 1600mg HCQ followed by 600mg daily doses are needed to reach concentrations relevant to SARS-CoV-2 inhibition within 72hours in≥60% (95% confidence interval: 49.5-69.0%) of COVID-19 patients.
DOI: 10.1016/j.therap.2021.01.056
PubMed: 33558079
PubMed Central: PMC7842207
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pubmed:33558079Le document en format XML
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Electronic address: noel.zahr@aphp.fr.</nlm:affiliation></affiliation></author><author><name sortKey="Urien, Saik" sort="Urien, Saik" uniqKey="Urien S" first="Saik" last="Urien">Saik Urien</name><affiliation><nlm:affiliation>AP-HP, Université de Paris, INSERM, Cochin Hospital, Department of Pediatric and Perinatal Pharmacology, 75014 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Llopis, Benoit" sort="Llopis, Benoit" uniqKey="Llopis B" first="Benoit" last="Llopis">Benoit Llopis</name><affiliation><nlm:affiliation>AP-HP, Sorbonne Université, Pitié-Salpêtrière Hospital, Department of Pharmacology and Clinical Investigation Center, INSERM, CIC-1901, Sorbonne Université, Faculty of Medicine, 75013 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Pourcher, Valerie" sort="Pourcher, Valerie" uniqKey="Pourcher V" first="Valérie" last="Pourcher">Valérie Pourcher</name><affiliation><nlm:affiliation>AP-HP, Sorbonne Université, INSERM 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France.</nlm:affiliation></affiliation></author><author><name sortKey="Mayaux, Julien" sort="Mayaux, Julien" uniqKey="Mayaux J" first="Julien" last="Mayaux">Julien Mayaux</name><affiliation><nlm:affiliation>AP-HP, Sorbonne Université, Service de Pneumologie, Médecine intensive - Réanimation (Département "R3S"), Groupe Hospitalier Universitaire Pitié-Salpêtrière-Charles-Foix, 75013 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Gandjbakhch, Estelle" sort="Gandjbakhch, Estelle" uniqKey="Gandjbakhch E" first="Estelle" last="Gandjbakhch">Estelle Gandjbakhch</name><affiliation><nlm:affiliation>AP-HP, Sorbonne Université, Service de Cardiologie, Groupe Hospitalier Universitaire Pitié-Salpêtrière-Charles-Foix, 75013 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Hekimian, Guillaume" sort="Hekimian, Guillaume" uniqKey="Hekimian G" first="Guillaume" last="Hekimian">Guillaume Hekimian</name><affiliation><nlm:affiliation>AP-HP, Sorbonne Université, Médecine intensive-Réanimation Médicale Groupe Hospitalier Universitaire Pitié-Salpêtrière-Charles-Foix, 75013 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Combes, Alain" sort="Combes, Alain" uniqKey="Combes A" first="Alain" last="Combes">Alain Combes</name><affiliation><nlm:affiliation>AP-HP, Sorbonne Université, Médecine intensive-Réanimation Médicale Groupe Hospitalier Universitaire Pitié-Salpêtrière-Charles-Foix, 75013 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Benveniste, Olivier" sort="Benveniste, Olivier" uniqKey="Benveniste O" first="Olivier" last="Benveniste">Olivier Benveniste</name><affiliation><nlm:affiliation>AP-HP, Sorbonne Université, Pitié-Salpêtrière Hospital, Department of Internal Medicine and Clinical Immunology, Centre de Référence des Maladies Auto-Immunes et Systémiques Rares, 75013 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Saadoun, David" sort="Saadoun, David" uniqKey="Saadoun D" first="David" last="Saadoun">David Saadoun</name><affiliation><nlm:affiliation>AP-HP, Sorbonne Université, Pitié-Salpêtrière Hospital, Department of Internal Medicine and Clinical Immunology, Centre de Référence des Maladies Auto-Immunes et Systémiques Rares, 75013 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Allenbach, Yves" sort="Allenbach, Yves" uniqKey="Allenbach Y" first="Yves" last="Allenbach">Yves Allenbach</name><affiliation><nlm:affiliation>AP-HP, Sorbonne Université, Pitié-Salpêtrière Hospital, Department of Internal Medicine and Clinical Immunology, Centre de Référence des Maladies Auto-Immunes et Systémiques Rares, 75013 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Pinna, Bruno" sort="Pinna, Bruno" uniqKey="Pinna B" first="Bruno" last="Pinna">Bruno Pinna</name><affiliation><nlm:affiliation>AP-HP, Sorbonne Université, Pitié-Salpêtrière Hospital, Department of Pharmacology and Clinical Investigation Center, INSERM, CIC-1901, Sorbonne Université, Faculty of Medicine, 75013 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Cacoub, Patrice" sort="Cacoub, Patrice" uniqKey="Cacoub P" first="Patrice" last="Cacoub">Patrice Cacoub</name><affiliation><nlm:affiliation>AP-HP, Sorbonne Université, Pitié-Salpêtrière Hospital, Department of Internal Medicine and Clinical Immunology, Centre de Référence des Maladies Auto-Immunes et Systémiques Rares, 75013 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Funck Brentano, Christian" sort="Funck Brentano, Christian" uniqKey="Funck Brentano C" first="Christian" last="Funck-Brentano">Christian Funck-Brentano</name><affiliation><nlm:affiliation>AP-HP, Sorbonne Université, Pitié-Salpêtrière Hospital, Department of Pharmacology and Clinical Investigation Center, INSERM, CIC-1901, Sorbonne Université, Faculty of Medicine, 75013 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Salem, Joe Elie" sort="Salem, Joe Elie" uniqKey="Salem J" first="Joe-Elie" last="Salem">Joe-Elie Salem</name><affiliation><nlm:affiliation>AP-HP, Sorbonne Université, Pitié-Salpêtrière Hospital, Department of Pharmacology and Clinical Investigation Center, INSERM, CIC-1901, Sorbonne Université, Faculty of Medicine, 75013 Paris, France.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2021">2021</date><idno type="RBID">pubmed:33558079</idno><idno type="pmid">33558079</idno><idno type="doi">10.1016/j.therap.2021.01.056</idno><idno type="pmc">PMC7842207</idno><idno type="wicri:Area/Main/Corpus">000363</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000363</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Pharmacokinetics and pharmacodynamics of hydroxychloroquine in hospitalized patients with COVID-19.</title><author><name sortKey="Zahr, Noel" sort="Zahr, Noel" uniqKey="Zahr N" first="Noël" last="Zahr">Noël Zahr</name><affiliation><nlm:affiliation>AP-HP, Sorbonne Université, Pitié-Salpêtrière Hospital, Department of Pharmacology and Clinical Investigation Center, INSERM, CIC-1901, Sorbonne Université, Faculty of Medicine, 75013 Paris, France. Electronic address: noel.zahr@aphp.fr.</nlm:affiliation></affiliation></author><author><name sortKey="Urien, Saik" sort="Urien, Saik" uniqKey="Urien S" first="Saik" last="Urien">Saik Urien</name><affiliation><nlm:affiliation>AP-HP, Université de Paris, INSERM, Cochin Hospital, Department of Pediatric and Perinatal Pharmacology, 75014 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Llopis, Benoit" sort="Llopis, Benoit" uniqKey="Llopis B" first="Benoit" last="Llopis">Benoit Llopis</name><affiliation><nlm:affiliation>AP-HP, Sorbonne Université, Pitié-Salpêtrière Hospital, Department of Pharmacology and Clinical Investigation Center, INSERM, CIC-1901, Sorbonne Université, Faculty of Medicine, 75013 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Pourcher, Valerie" sort="Pourcher, Valerie" uniqKey="Pourcher V" first="Valérie" last="Pourcher">Valérie Pourcher</name><affiliation><nlm:affiliation>AP-HP, Sorbonne Université, INSERM 1136, Institut Pierre-Louis d'Épidémiologie et de Santé Publique, Pitié-Salpêtrière Hospital, Service de Maladies Infectieuses et Tropicales, 75013 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Paccoud, Olivier" sort="Paccoud, Olivier" uniqKey="Paccoud O" first="Olivier" last="Paccoud">Olivier Paccoud</name><affiliation><nlm:affiliation>AP-HP, Sorbonne Université, INSERM 1136, Institut Pierre-Louis d'Épidémiologie et de Santé Publique, Pitié-Salpêtrière Hospital, Service de Maladies Infectieuses et Tropicales, 75013 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Bleibtreu, Alexandre" sort="Bleibtreu, Alexandre" uniqKey="Bleibtreu A" first="Alexandre" last="Bleibtreu">Alexandre Bleibtreu</name><affiliation><nlm:affiliation>AP-HP, Sorbonne Université, INSERM 1136, Institut Pierre-Louis d'Épidémiologie et de Santé Publique, Pitié-Salpêtrière Hospital, Service de Maladies Infectieuses et Tropicales, 75013 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Mayaux, Julien" sort="Mayaux, Julien" uniqKey="Mayaux J" first="Julien" last="Mayaux">Julien Mayaux</name><affiliation><nlm:affiliation>AP-HP, Sorbonne Université, Service de Pneumologie, Médecine intensive - Réanimation (Département "R3S"), Groupe Hospitalier Universitaire Pitié-Salpêtrière-Charles-Foix, 75013 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Gandjbakhch, Estelle" sort="Gandjbakhch, Estelle" uniqKey="Gandjbakhch E" first="Estelle" last="Gandjbakhch">Estelle Gandjbakhch</name><affiliation><nlm:affiliation>AP-HP, Sorbonne Université, Service de Cardiologie, Groupe Hospitalier Universitaire Pitié-Salpêtrière-Charles-Foix, 75013 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Hekimian, Guillaume" sort="Hekimian, Guillaume" uniqKey="Hekimian G" first="Guillaume" last="Hekimian">Guillaume Hekimian</name><affiliation><nlm:affiliation>AP-HP, Sorbonne Université, Médecine intensive-Réanimation Médicale Groupe Hospitalier Universitaire Pitié-Salpêtrière-Charles-Foix, 75013 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Combes, Alain" sort="Combes, Alain" uniqKey="Combes A" first="Alain" last="Combes">Alain Combes</name><affiliation><nlm:affiliation>AP-HP, Sorbonne Université, Médecine intensive-Réanimation Médicale Groupe Hospitalier Universitaire Pitié-Salpêtrière-Charles-Foix, 75013 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Benveniste, Olivier" sort="Benveniste, Olivier" uniqKey="Benveniste O" first="Olivier" last="Benveniste">Olivier Benveniste</name><affiliation><nlm:affiliation>AP-HP, Sorbonne Université, Pitié-Salpêtrière Hospital, Department of Internal Medicine and Clinical Immunology, Centre de Référence des Maladies Auto-Immunes et Systémiques Rares, 75013 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Saadoun, David" sort="Saadoun, David" uniqKey="Saadoun D" first="David" last="Saadoun">David Saadoun</name><affiliation><nlm:affiliation>AP-HP, Sorbonne Université, Pitié-Salpêtrière Hospital, Department of Internal Medicine and Clinical Immunology, Centre de Référence des Maladies Auto-Immunes et Systémiques Rares, 75013 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Allenbach, Yves" sort="Allenbach, Yves" uniqKey="Allenbach Y" first="Yves" last="Allenbach">Yves Allenbach</name><affiliation><nlm:affiliation>AP-HP, Sorbonne Université, Pitié-Salpêtrière Hospital, Department of Internal Medicine and Clinical Immunology, Centre de Référence des Maladies Auto-Immunes et Systémiques Rares, 75013 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Pinna, Bruno" sort="Pinna, Bruno" uniqKey="Pinna B" first="Bruno" last="Pinna">Bruno Pinna</name><affiliation><nlm:affiliation>AP-HP, Sorbonne Université, Pitié-Salpêtrière Hospital, Department of Pharmacology and Clinical Investigation Center, INSERM, CIC-1901, Sorbonne Université, Faculty of Medicine, 75013 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Cacoub, Patrice" sort="Cacoub, Patrice" uniqKey="Cacoub P" first="Patrice" last="Cacoub">Patrice Cacoub</name><affiliation><nlm:affiliation>AP-HP, Sorbonne Université, Pitié-Salpêtrière Hospital, Department of Internal Medicine and Clinical Immunology, Centre de Référence des Maladies Auto-Immunes et Systémiques Rares, 75013 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Funck Brentano, Christian" sort="Funck Brentano, Christian" uniqKey="Funck Brentano C" first="Christian" last="Funck-Brentano">Christian Funck-Brentano</name><affiliation><nlm:affiliation>AP-HP, Sorbonne Université, Pitié-Salpêtrière Hospital, Department of Pharmacology and Clinical Investigation Center, INSERM, CIC-1901, Sorbonne Université, Faculty of Medicine, 75013 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Salem, Joe Elie" sort="Salem, Joe Elie" uniqKey="Salem J" first="Joe-Elie" last="Salem">Joe-Elie Salem</name><affiliation><nlm:affiliation>AP-HP, Sorbonne Université, Pitié-Salpêtrière Hospital, Department of Pharmacology and Clinical Investigation Center, INSERM, CIC-1901, Sorbonne Université, Faculty of Medicine, 75013 Paris, France.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Therapie</title><idno type="eISSN">1958-5578</idno><imprint><date when="2021" type="published">2021</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><b>BACKGROUND</b></p><p>Hydroxychloroquine (HCQ) dosage required to reach circulating levels that inhibit SARS-Cov-2 are extrapolated from pharmacokinetic data in non-COVID-19 patients.</p></div><div type="abstract" xml:lang="en"><p><b>METHODS</b></p><p>We performed a population-pharmacokinetic analysis from 104 consecutive COVID-19 hospitalized patients (31 in intensive care units, 73 in medical wards, n=149 samples). Plasma HCQ concentration were measured using high performance liquid chromatography with fluorometric detection. Modelling used Monolix-2019R2.</p></div><div type="abstract" xml:lang="en"><p><b>RESULTS</b></p><p>HCQ doses ranged from 200 to 800mg/day administered for 1 to 11days and median HCQ plasma concentration was 151ng/mL. Among the tested covariates, only bodyweight influenced elimination oral clearance (CL) and apparent volume of distribution (Vd). CL/F (F for unknown bioavailability) and Vd/F (relative standard-error, %) estimates were 45.9L/h (21.2) and 6690L (16.1). The derived elimination half-life (t1/2) was 102h. These parameters in COVID-19 differed from those reported in patients with lupus, where CL/F, Vd/F and t1/2 are reported to be 68L/h, 2440 L and 19.5h, respectively. Within 72h of HCQ initiation, only 16/104 (15.4%) COVID-19 patients had HCQ plasma levels above the in vitro half maximal effective concentration of HCQ against SARS-CoV-2 (240ng/mL). HCQ did not influence inflammation status (assessed by C-reactive protein) or SARS-CoV-2 viral clearance (assessed by real-time reverse transcription-PCR nasopharyngeal swabs).</p></div><div type="abstract" xml:lang="en"><p><b>CONCLUSION</b></p><p>The interindividual variability of HCQ pharmacokinetic parameters in severe COVID-19 patients was important and differed from that previously reported in non-COVID-19 patients. Loading doses of 1600mg HCQ followed by 600mg daily doses are needed to reach concentrations relevant to SARS-CoV-2 inhibition within 72hours in≥60% (95% confidence interval: 49.5-69.0%) of COVID-19 patients.</p></div></front></TEI><pubmed><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">33558079</PMID><DateRevised><Year>2021</Year><Month>02</Month><Day>22</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1958-5578</ISSN><JournalIssue CitedMedium="Internet"><PubDate><Year>2021</Year><Month>Jan</Month><Day>28</Day></PubDate></JournalIssue><Title>Therapie</Title><ISOAbbreviation>Therapie</ISOAbbreviation></Journal><ArticleTitle>Pharmacokinetics and pharmacodynamics of hydroxychloroquine in hospitalized patients with COVID-19.</ArticleTitle><ELocationID EIdType="pii" ValidYN="Y">S0040-5957(21)00066-4</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.therap.2021.01.056</ELocationID><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Hydroxychloroquine (HCQ) dosage required to reach circulating levels that inhibit SARS-Cov-2 are extrapolated from pharmacokinetic data in non-COVID-19 patients.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">We performed a population-pharmacokinetic analysis from 104 consecutive COVID-19 hospitalized patients (31 in intensive care units, 73 in medical wards, n=149 samples). Plasma HCQ concentration were measured using high performance liquid chromatography with fluorometric detection. Modelling used Monolix-2019R2.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">HCQ doses ranged from 200 to 800mg/day administered for 1 to 11days and median HCQ plasma concentration was 151ng/mL. Among the tested covariates, only bodyweight influenced elimination oral clearance (CL) and apparent volume of distribution (Vd). CL/F (F for unknown bioavailability) and Vd/F (relative standard-error, %) estimates were 45.9L/h (21.2) and 6690L (16.1). The derived elimination half-life (t1/2) was 102h. These parameters in COVID-19 differed from those reported in patients with lupus, where CL/F, Vd/F and t1/2 are reported to be 68L/h, 2440 L and 19.5h, respectively. Within 72h of HCQ initiation, only 16/104 (15.4%) COVID-19 patients had HCQ plasma levels above the in vitro half maximal effective concentration of HCQ against SARS-CoV-2 (240ng/mL). HCQ did not influence inflammation status (assessed by C-reactive protein) or SARS-CoV-2 viral clearance (assessed by real-time reverse transcription-PCR nasopharyngeal swabs).</AbstractText><AbstractText Label="CONCLUSION" NlmCategory="CONCLUSIONS">The interindividual variability of HCQ pharmacokinetic parameters in severe COVID-19 patients was important and differed from that previously reported in non-COVID-19 patients. Loading doses of 1600mg HCQ followed by 600mg daily doses are needed to reach concentrations relevant to SARS-CoV-2 inhibition within 72hours in≥60% (95% confidence interval: 49.5-69.0%) of COVID-19 patients.</AbstractText><CopyrightInformation>Copyright © 2021 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Zahr</LastName><ForeName>Noël</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>AP-HP, Sorbonne Université, Pitié-Salpêtrière Hospital, Department of Pharmacology and Clinical Investigation Center, INSERM, CIC-1901, Sorbonne Université, Faculty of Medicine, 75013 Paris, France. Electronic address: noel.zahr@aphp.fr.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Urien</LastName><ForeName>Saik</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>AP-HP, Université de Paris, INSERM, Cochin Hospital, Department of Pediatric and Perinatal Pharmacology, 75014 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Llopis</LastName><ForeName>Benoit</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>AP-HP, Sorbonne Université, Pitié-Salpêtrière Hospital, Department of Pharmacology and Clinical Investigation Center, INSERM, CIC-1901, Sorbonne Université, Faculty of Medicine, 75013 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pourcher</LastName><ForeName>Valérie</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>AP-HP, Sorbonne Université, INSERM 1136, Institut Pierre-Louis d'Épidémiologie et de Santé Publique, Pitié-Salpêtrière Hospital, Service de Maladies Infectieuses et Tropicales, 75013 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Paccoud</LastName><ForeName>Olivier</ForeName><Initials>O</Initials><AffiliationInfo><Affiliation>AP-HP, Sorbonne Université, INSERM 1136, Institut Pierre-Louis d'Épidémiologie et de Santé Publique, Pitié-Salpêtrière Hospital, Service de Maladies Infectieuses et Tropicales, 75013 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bleibtreu</LastName><ForeName>Alexandre</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>AP-HP, Sorbonne Université, INSERM 1136, Institut Pierre-Louis d'Épidémiologie et de Santé Publique, Pitié-Salpêtrière Hospital, Service de Maladies Infectieuses et Tropicales, 75013 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mayaux</LastName><ForeName>Julien</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>AP-HP, Sorbonne Université, Service de Pneumologie, Médecine intensive - Réanimation (Département "R3S"), Groupe Hospitalier Universitaire Pitié-Salpêtrière-Charles-Foix, 75013 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gandjbakhch</LastName><ForeName>Estelle</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>AP-HP, Sorbonne Université, Service de Cardiologie, Groupe Hospitalier Universitaire Pitié-Salpêtrière-Charles-Foix, 75013 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hekimian</LastName><ForeName>Guillaume</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>AP-HP, Sorbonne Université, Médecine intensive-Réanimation Médicale Groupe Hospitalier Universitaire Pitié-Salpêtrière-Charles-Foix, 75013 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Combes</LastName><ForeName>Alain</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>AP-HP, Sorbonne Université, Médecine intensive-Réanimation Médicale Groupe Hospitalier Universitaire Pitié-Salpêtrière-Charles-Foix, 75013 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Benveniste</LastName><ForeName>Olivier</ForeName><Initials>O</Initials><AffiliationInfo><Affiliation>AP-HP, Sorbonne Université, Pitié-Salpêtrière Hospital, Department of Internal Medicine and Clinical Immunology, Centre de Référence des Maladies Auto-Immunes et Systémiques Rares, 75013 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Saadoun</LastName><ForeName>David</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>AP-HP, Sorbonne Université, Pitié-Salpêtrière Hospital, Department of Internal Medicine and Clinical Immunology, Centre de Référence des Maladies Auto-Immunes et Systémiques Rares, 75013 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Allenbach</LastName><ForeName>Yves</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>AP-HP, Sorbonne Université, Pitié-Salpêtrière Hospital, Department of Internal Medicine and Clinical Immunology, Centre de Référence des Maladies Auto-Immunes et Systémiques Rares, 75013 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pinna</LastName><ForeName>Bruno</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>AP-HP, Sorbonne Université, Pitié-Salpêtrière Hospital, Department of Pharmacology and Clinical Investigation Center, INSERM, CIC-1901, Sorbonne Université, Faculty of Medicine, 75013 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cacoub</LastName><ForeName>Patrice</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>AP-HP, Sorbonne Université, Pitié-Salpêtrière Hospital, Department of Internal Medicine and Clinical Immunology, Centre de Référence des Maladies Auto-Immunes et Systémiques Rares, 75013 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Funck-Brentano</LastName><ForeName>Christian</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>AP-HP, Sorbonne Université, Pitié-Salpêtrière Hospital, Department of Pharmacology and Clinical Investigation Center, INSERM, CIC-1901, Sorbonne Université, Faculty of Medicine, 75013 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Salem</LastName><ForeName>Joe-Elie</ForeName><Initials>JE</Initials><AffiliationInfo><Affiliation>AP-HP, Sorbonne Université, Pitié-Salpêtrière Hospital, Department of Pharmacology and Clinical Investigation Center, INSERM, CIC-1901, Sorbonne Université, Faculty of Medicine, 75013 Paris, France.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2021</Year><Month>01</Month><Day>28</Day></ArticleDate></Article><MedlineJournalInfo><Country>France</Country><MedlineTA>Therapie</MedlineTA><NlmUniqueID>0420544</NlmUniqueID><ISSNLinking>0040-5957</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">COVID-19</Keyword><Keyword MajorTopicYN="N">Hydroxychloroquine</Keyword><Keyword MajorTopicYN="N">Pharmacodynamics</Keyword><Keyword MajorTopicYN="N">Pharmacokinetics</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>11</Month><Day>17</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2021</Year><Month>01</Month><Day>03</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2021</Year><Month>01</Month><Day>22</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2021</Year><Month>2</Month><Day>10</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2021</Year><Month>2</Month><Day>10</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2021</Year><Month>2</Month><Day>9</Day><Hour>5</Hour><Minute>58</Minute></PubMedPubDate></History><PublicationStatus>aheadofprint</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">33558079</ArticleId><ArticleId IdType="pii">S0040-5957(21)00066-4</ArticleId><ArticleId IdType="doi">10.1016/j.therap.2021.01.056</ArticleId><ArticleId IdType="pmc">PMC7842207</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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