CovidChloroV1, Main, Corpus, bibRecord, 001200

Effect of Systemic Inflammatory Response to SARS-CoV-2 on Lopinavir and Hydroxychloroquine Plasma Concentrations.

Identifieur interne : 001200 ( Main/Corpus ); précédent : 001199; suivant : 001201

Effect of Systemic Inflammatory Response to SARS-CoV-2 on Lopinavir and Hydroxychloroquine Plasma Concentrations.

Auteurs : Catia Marzolini ; Felix Stader ; Marcel Stoeckle ; Fabian Franzeck ; Adrian Egli ; Stefano Bassetti ; Alexa Hollinger ; Michael Osthoff ; Maja Weisser ; Caroline E. Gebhard ; Veronika Baettig ; Julia Geenen ; Nina Khanna ; Sarah Tschudin-Sutter ; Daniel Mueller ; Hans H. Hirsch ; Manuel Battegay ; Parham Sendi

Source :

Antimicrobial agents and chemotherapy [ 1098-6596 ] ; 2020.

RBID : pubmed:32641296

English descriptors

KwdEn :
- Adult (MeSH), Aged (MeSH), Aged, 80 and over (MeSH), Antibodies, Monoclonal, Humanized (therapeutic use), Antiviral Agents (blood), Antiviral Agents (pharmacokinetics), Antiviral Agents (pharmacology), Betacoronavirus (drug effects), Betacoronavirus (immunology), Betacoronavirus (pathogenicity), Biomarkers (blood), C-Reactive Protein (metabolism), COVID-19 (MeSH), Coronavirus Infections (drug therapy), Coronavirus Infections (immunology), Coronavirus Infections (mortality), Coronavirus Infections (virology), Cytokine Release Syndrome (drug therapy), Cytokine Release Syndrome (immunology), Cytokine Release Syndrome (mortality), Cytokine Release Syndrome (virology), Drug Administration Schedule (MeSH), Drug Combinations (MeSH), Female (MeSH), Hospitals, University (MeSH), Humans (MeSH), Hydroxychloroquine (blood), Hydroxychloroquine (pharmacokinetics), Hydroxychloroquine (pharmacology), Length of Stay (statistics & numerical data), Lopinavir (blood), Lopinavir (pharmacokinetics), Lopinavir (pharmacology), Male (MeSH), Middle Aged (MeSH), Pandemics (MeSH), Pneumonia, Viral (drug therapy), Pneumonia, Viral (immunology), Pneumonia, Viral (mortality), Pneumonia, Viral (virology), Retrospective Studies (MeSH), Ritonavir (blood), Ritonavir (pharmacokinetics), Ritonavir (pharmacology), SARS-CoV-2 (MeSH), Severity of Illness Index (MeSH), Survival Analysis (MeSH).
MESH :
- chemical , blood : Antiviral Agents, Biomarkers, Hydroxychloroquine, Lopinavir, Ritonavir.
- chemical , metabolism : C-Reactive Protein.
- chemical , pharmacokinetics : Antiviral Agents, Hydroxychloroquine, Lopinavir, Ritonavir.
- chemical , pharmacology : Antiviral Agents, Hydroxychloroquine, Lopinavir, Ritonavir.
- chemical , therapeutic use : Antibodies, Monoclonal, Humanized.
- drug effects : Betacoronavirus.
- drug therapy : Coronavirus Infections, Cytokine Release Syndrome, Pneumonia, Viral.
- immunology : Betacoronavirus, Coronavirus Infections, Cytokine Release Syndrome, Pneumonia, Viral.
- mortality : Coronavirus Infections, Cytokine Release Syndrome, Pneumonia, Viral.
- pathogenicity : Betacoronavirus.
- statistics & numerical data : Length of Stay.
- virology : Coronavirus Infections, Cytokine Release Syndrome, Pneumonia, Viral.
- Adult, Aged, Aged, 80 and over, COVID-19, Drug Administration Schedule, Drug Combinations, Female, Hospitals, University, Humans, Male, Middle Aged, Pandemics, Retrospective Studies, SARS-CoV-2, Severity of Illness Index, Survival Analysis.

Abstract

Coronavirus disease 2019 (COVID-19) leads to inflammatory cytokine release, which can downregulate the expression of metabolizing enzymes. This cascade affects drug concentrations in the plasma. We investigated the association between lopinavir (LPV) and hydroxychloroquine (HCQ) plasma concentrations and the levels of the acute-phase inflammation marker C-reactive protein (CRP). LPV plasma concentrations in 92 patients hospitalized at our institution were prospectively collected. Lopinavir-ritonavir was administered every 12 hours, 800/200 mg on day 1 and 400/100 mg on day 2 until day 5 or 7. HCQ was given at 800 mg, followed by 400 mg after 6, 24, and 48 h. Hematological, liver, kidney, and inflammation laboratory values were analyzed on the day of drug level determination. The median age of study participants was 59 (range, 24 to 85) years, and 71% were male. The median durations from symptom onset to hospitalization and treatment initiation were 7 days (interquartile range [IQR], 4 to 10) and 8 days (IQR, 5 to 10), respectively. The median LPV trough concentration on day 3 of treatment was 26.5 μg/ml (IQR, 18.9 to 31.5). LPV plasma concentrations positively correlated with CRP values (r = 0.37, P < 0.001) and were significantly lower when tocilizumab was preadministered. No correlation was found between HCQ concentrations and CRP values. High LPV plasma concentrations were observed in COVID-19 patients. The ratio of calculated unbound drug fraction to published SARS-CoV-2 50% effective concentrations (EC₅₀) indicated insufficient LPV concentrations in the lung. CRP values significantly correlated with LPV but not HCQ plasma concentrations, implying inhibition of cytochrome P450 3A4 (CYP3A4) metabolism by inflammation.

DOI: 10.1128/AAC.01177-20
PubMed: 32641296
PubMed Central: PMC7449226

Links to Exploration step

pubmed:32641296

Le document en format XML

<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Effect of Systemic Inflammatory Response to SARS-CoV-2 on Lopinavir and Hydroxychloroquine Plasma Concentrations.</title>
<author><name sortKey="Marzolini, Catia" sort="Marzolini, Catia" uniqKey="Marzolini C" first="Catia" last="Marzolini">Catia Marzolini</name>
<affiliation><nlm:affiliation>Division of Infectious Diseases & Hospital Hygiene, University Hospital Basel and University of Basel, Basel, Switzerland catia.marzolini@usb.ch parham.sendi@usb.ch.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Stader, Felix" sort="Stader, Felix" uniqKey="Stader F" first="Felix" last="Stader">Felix Stader</name>
<affiliation><nlm:affiliation>Division of Infectious Diseases & Hospital Hygiene, University Hospital Basel and University of Basel, Basel, Switzerland.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Stoeckle, Marcel" sort="Stoeckle, Marcel" uniqKey="Stoeckle M" first="Marcel" last="Stoeckle">Marcel Stoeckle</name>
<affiliation><nlm:affiliation>Division of Infectious Diseases & Hospital Hygiene, University Hospital Basel and University of Basel, Basel, Switzerland.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Franzeck, Fabian" sort="Franzeck, Fabian" uniqKey="Franzeck F" first="Fabian" last="Franzeck">Fabian Franzeck</name>
<affiliation><nlm:affiliation>Division of Infectious Diseases & Hospital Hygiene, University Hospital Basel and University of Basel, Basel, Switzerland.</nlm:affiliation>
</affiliation>
<affiliation><nlm:affiliation>Research and Analysis Services, University Hospital Basel and University of Basel, Basel, Switzerland.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Egli, Adrian" sort="Egli, Adrian" uniqKey="Egli A" first="Adrian" last="Egli">Adrian Egli</name>
<affiliation><nlm:affiliation>Division of Clinical Bacteriology and Mycology, University Hospital Basel, Basel, Switzerland.</nlm:affiliation>
</affiliation>
<affiliation><nlm:affiliation>Applied Microbiology Research, Department of Biomedicine, University of Basel, Basel, Switzerland.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Bassetti, Stefano" sort="Bassetti, Stefano" uniqKey="Bassetti S" first="Stefano" last="Bassetti">Stefano Bassetti</name>
<affiliation><nlm:affiliation>Division of Internal Medicine and Department of Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Hollinger, Alexa" sort="Hollinger, Alexa" uniqKey="Hollinger A" first="Alexa" last="Hollinger">Alexa Hollinger</name>
<affiliation><nlm:affiliation>Intensive Care Unit, University Hospital Basel, Basel, Switzerland.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Osthoff, Michael" sort="Osthoff, Michael" uniqKey="Osthoff M" first="Michael" last="Osthoff">Michael Osthoff</name>
<affiliation><nlm:affiliation>Division of Internal Medicine and Department of Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Weisser, Maja" sort="Weisser, Maja" uniqKey="Weisser M" first="Maja" last="Weisser">Maja Weisser</name>
<affiliation><nlm:affiliation>Division of Infectious Diseases & Hospital Hygiene, University Hospital Basel and University of Basel, Basel, Switzerland.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Gebhard, Caroline E" sort="Gebhard, Caroline E" uniqKey="Gebhard C" first="Caroline E" last="Gebhard">Caroline E. Gebhard</name>
<affiliation><nlm:affiliation>Intensive Care Unit, University Hospital Basel, Basel, Switzerland.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Baettig, Veronika" sort="Baettig, Veronika" uniqKey="Baettig V" first="Veronika" last="Baettig">Veronika Baettig</name>
<affiliation><nlm:affiliation>Division of Infectious Diseases & Hospital Hygiene, University Hospital Basel and University of Basel, Basel, Switzerland.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Geenen, Julia" sort="Geenen, Julia" uniqKey="Geenen J" first="Julia" last="Geenen">Julia Geenen</name>
<affiliation><nlm:affiliation>Division of Internal Medicine and Department of Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Khanna, Nina" sort="Khanna, Nina" uniqKey="Khanna N" first="Nina" last="Khanna">Nina Khanna</name>
<affiliation><nlm:affiliation>Division of Infectious Diseases & Hospital Hygiene, University Hospital Basel and University of Basel, Basel, Switzerland.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Tschudin Sutter, Sarah" sort="Tschudin Sutter, Sarah" uniqKey="Tschudin Sutter S" first="Sarah" last="Tschudin-Sutter">Sarah Tschudin-Sutter</name>
<affiliation><nlm:affiliation>Division of Infectious Diseases & Hospital Hygiene, University Hospital Basel and University of Basel, Basel, Switzerland.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Mueller, Daniel" sort="Mueller, Daniel" uniqKey="Mueller D" first="Daniel" last="Mueller">Daniel Mueller</name>
<affiliation><nlm:affiliation>Institute of Clinical Chemistry, University Hospital Zurich, Zurich, Switzerland.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Hirsch, Hans H" sort="Hirsch, Hans H" uniqKey="Hirsch H" first="Hans H" last="Hirsch">Hans H. Hirsch</name>
<affiliation><nlm:affiliation>Division of Infectious Diseases & Hospital Hygiene, University Hospital Basel and University of Basel, Basel, Switzerland.</nlm:affiliation>
</affiliation>
<affiliation><nlm:affiliation>Transplantation & Clinical Virology, Department of Biomedicine, University of Basel, Basel, Switzerland.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Battegay, Manuel" sort="Battegay, Manuel" uniqKey="Battegay M" first="Manuel" last="Battegay">Manuel Battegay</name>
<affiliation><nlm:affiliation>Division of Infectious Diseases & Hospital Hygiene, University Hospital Basel and University of Basel, Basel, Switzerland.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Sendi, Parham" sort="Sendi, Parham" uniqKey="Sendi P" first="Parham" last="Sendi">Parham Sendi</name>
<affiliation><nlm:affiliation>Division of Infectious Diseases & Hospital Hygiene, University Hospital Basel and University of Basel, Basel, Switzerland catia.marzolini@usb.ch parham.sendi@usb.ch.</nlm:affiliation>
</affiliation>
<affiliation><nlm:affiliation>Institute for Infectious Diseases, University of Bern, Bern, Switzerland.</nlm:affiliation>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PubMed</idno>
<date when="2020">2020</date>
<idno type="RBID">pubmed:32641296</idno>
<idno type="pmid">32641296</idno>
<idno type="doi">10.1128/AAC.01177-20</idno>
<idno type="pmc">PMC7449226</idno>
<idno type="wicri:Area/Main/Corpus">001200</idno>
<idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">001200</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">Effect of Systemic Inflammatory Response to SARS-CoV-2 on Lopinavir and Hydroxychloroquine Plasma Concentrations.</title>
<author><name sortKey="Marzolini, Catia" sort="Marzolini, Catia" uniqKey="Marzolini C" first="Catia" last="Marzolini">Catia Marzolini</name>
<affiliation><nlm:affiliation>Division of Infectious Diseases & Hospital Hygiene, University Hospital Basel and University of Basel, Basel, Switzerland catia.marzolini@usb.ch parham.sendi@usb.ch.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Stader, Felix" sort="Stader, Felix" uniqKey="Stader F" first="Felix" last="Stader">Felix Stader</name>
<affiliation><nlm:affiliation>Division of Infectious Diseases & Hospital Hygiene, University Hospital Basel and University of Basel, Basel, Switzerland.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Stoeckle, Marcel" sort="Stoeckle, Marcel" uniqKey="Stoeckle M" first="Marcel" last="Stoeckle">Marcel Stoeckle</name>
<affiliation><nlm:affiliation>Division of Infectious Diseases & Hospital Hygiene, University Hospital Basel and University of Basel, Basel, Switzerland.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Franzeck, Fabian" sort="Franzeck, Fabian" uniqKey="Franzeck F" first="Fabian" last="Franzeck">Fabian Franzeck</name>
<affiliation><nlm:affiliation>Division of Infectious Diseases & Hospital Hygiene, University Hospital Basel and University of Basel, Basel, Switzerland.</nlm:affiliation>
</affiliation>
<affiliation><nlm:affiliation>Research and Analysis Services, University Hospital Basel and University of Basel, Basel, Switzerland.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Egli, Adrian" sort="Egli, Adrian" uniqKey="Egli A" first="Adrian" last="Egli">Adrian Egli</name>
<affiliation><nlm:affiliation>Division of Clinical Bacteriology and Mycology, University Hospital Basel, Basel, Switzerland.</nlm:affiliation>
</affiliation>
<affiliation><nlm:affiliation>Applied Microbiology Research, Department of Biomedicine, University of Basel, Basel, Switzerland.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Bassetti, Stefano" sort="Bassetti, Stefano" uniqKey="Bassetti S" first="Stefano" last="Bassetti">Stefano Bassetti</name>
<affiliation><nlm:affiliation>Division of Internal Medicine and Department of Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Hollinger, Alexa" sort="Hollinger, Alexa" uniqKey="Hollinger A" first="Alexa" last="Hollinger">Alexa Hollinger</name>
<affiliation><nlm:affiliation>Intensive Care Unit, University Hospital Basel, Basel, Switzerland.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Osthoff, Michael" sort="Osthoff, Michael" uniqKey="Osthoff M" first="Michael" last="Osthoff">Michael Osthoff</name>
<affiliation><nlm:affiliation>Division of Internal Medicine and Department of Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Weisser, Maja" sort="Weisser, Maja" uniqKey="Weisser M" first="Maja" last="Weisser">Maja Weisser</name>
<affiliation><nlm:affiliation>Division of Infectious Diseases & Hospital Hygiene, University Hospital Basel and University of Basel, Basel, Switzerland.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Gebhard, Caroline E" sort="Gebhard, Caroline E" uniqKey="Gebhard C" first="Caroline E" last="Gebhard">Caroline E. Gebhard</name>
<affiliation><nlm:affiliation>Intensive Care Unit, University Hospital Basel, Basel, Switzerland.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Baettig, Veronika" sort="Baettig, Veronika" uniqKey="Baettig V" first="Veronika" last="Baettig">Veronika Baettig</name>
<affiliation><nlm:affiliation>Division of Infectious Diseases & Hospital Hygiene, University Hospital Basel and University of Basel, Basel, Switzerland.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Geenen, Julia" sort="Geenen, Julia" uniqKey="Geenen J" first="Julia" last="Geenen">Julia Geenen</name>
<affiliation><nlm:affiliation>Division of Internal Medicine and Department of Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Khanna, Nina" sort="Khanna, Nina" uniqKey="Khanna N" first="Nina" last="Khanna">Nina Khanna</name>
<affiliation><nlm:affiliation>Division of Infectious Diseases & Hospital Hygiene, University Hospital Basel and University of Basel, Basel, Switzerland.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Tschudin Sutter, Sarah" sort="Tschudin Sutter, Sarah" uniqKey="Tschudin Sutter S" first="Sarah" last="Tschudin-Sutter">Sarah Tschudin-Sutter</name>
<affiliation><nlm:affiliation>Division of Infectious Diseases & Hospital Hygiene, University Hospital Basel and University of Basel, Basel, Switzerland.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Mueller, Daniel" sort="Mueller, Daniel" uniqKey="Mueller D" first="Daniel" last="Mueller">Daniel Mueller</name>
<affiliation><nlm:affiliation>Institute of Clinical Chemistry, University Hospital Zurich, Zurich, Switzerland.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Hirsch, Hans H" sort="Hirsch, Hans H" uniqKey="Hirsch H" first="Hans H" last="Hirsch">Hans H. Hirsch</name>
<affiliation><nlm:affiliation>Division of Infectious Diseases & Hospital Hygiene, University Hospital Basel and University of Basel, Basel, Switzerland.</nlm:affiliation>
</affiliation>
<affiliation><nlm:affiliation>Transplantation & Clinical Virology, Department of Biomedicine, University of Basel, Basel, Switzerland.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Battegay, Manuel" sort="Battegay, Manuel" uniqKey="Battegay M" first="Manuel" last="Battegay">Manuel Battegay</name>
<affiliation><nlm:affiliation>Division of Infectious Diseases & Hospital Hygiene, University Hospital Basel and University of Basel, Basel, Switzerland.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Sendi, Parham" sort="Sendi, Parham" uniqKey="Sendi P" first="Parham" last="Sendi">Parham Sendi</name>
<affiliation><nlm:affiliation>Division of Infectious Diseases & Hospital Hygiene, University Hospital Basel and University of Basel, Basel, Switzerland catia.marzolini@usb.ch parham.sendi@usb.ch.</nlm:affiliation>
</affiliation>
<affiliation><nlm:affiliation>Institute for Infectious Diseases, University of Bern, Bern, Switzerland.</nlm:affiliation>
</affiliation>
</author>
</analytic>
<series><title level="j">Antimicrobial agents and chemotherapy</title>
<idno type="eISSN">1098-6596</idno>
<imprint><date when="2020" type="published">2020</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult (MeSH)</term>
<term>Aged (MeSH)</term>
<term>Aged, 80 and over (MeSH)</term>
<term>Antibodies, Monoclonal, Humanized (therapeutic use)</term>
<term>Antiviral Agents (blood)</term>
<term>Antiviral Agents (pharmacokinetics)</term>
<term>Antiviral Agents (pharmacology)</term>
<term>Betacoronavirus (drug effects)</term>
<term>Betacoronavirus (immunology)</term>
<term>Betacoronavirus (pathogenicity)</term>
<term>Biomarkers (blood)</term>
<term>C-Reactive Protein (metabolism)</term>
<term>COVID-19 (MeSH)</term>
<term>Coronavirus Infections (drug therapy)</term>
<term>Coronavirus Infections (immunology)</term>
<term>Coronavirus Infections (mortality)</term>
<term>Coronavirus Infections (virology)</term>
<term>Cytokine Release Syndrome (drug therapy)</term>
<term>Cytokine Release Syndrome (immunology)</term>
<term>Cytokine Release Syndrome (mortality)</term>
<term>Cytokine Release Syndrome (virology)</term>
<term>Drug Administration Schedule (MeSH)</term>
<term>Drug Combinations (MeSH)</term>
<term>Female (MeSH)</term>
<term>Hospitals, University (MeSH)</term>
<term>Humans (MeSH)</term>
<term>Hydroxychloroquine (blood)</term>
<term>Hydroxychloroquine (pharmacokinetics)</term>
<term>Hydroxychloroquine (pharmacology)</term>
<term>Length of Stay (statistics & numerical data)</term>
<term>Lopinavir (blood)</term>
<term>Lopinavir (pharmacokinetics)</term>
<term>Lopinavir (pharmacology)</term>
<term>Male (MeSH)</term>
<term>Middle Aged (MeSH)</term>
<term>Pandemics (MeSH)</term>
<term>Pneumonia, Viral (drug therapy)</term>
<term>Pneumonia, Viral (immunology)</term>
<term>Pneumonia, Viral (mortality)</term>
<term>Pneumonia, Viral (virology)</term>
<term>Retrospective Studies (MeSH)</term>
<term>Ritonavir (blood)</term>
<term>Ritonavir (pharmacokinetics)</term>
<term>Ritonavir (pharmacology)</term>
<term>SARS-CoV-2 (MeSH)</term>
<term>Severity of Illness Index (MeSH)</term>
<term>Survival Analysis (MeSH)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Antiviral Agents</term>
<term>Biomarkers</term>
<term>Hydroxychloroquine</term>
<term>Lopinavir</term>
<term>Ritonavir</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>C-Reactive Protein</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Antiviral Agents</term>
<term>Hydroxychloroquine</term>
<term>Lopinavir</term>
<term>Ritonavir</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiviral Agents</term>
<term>Hydroxychloroquine</term>
<term>Lopinavir</term>
<term>Ritonavir</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antibodies, Monoclonal, Humanized</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Betacoronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Coronavirus Infections</term>
<term>Cytokine Release Syndrome</term>
<term>Pneumonia, Viral</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Betacoronavirus</term>
<term>Coronavirus Infections</term>
<term>Cytokine Release Syndrome</term>
<term>Pneumonia, Viral</term>
</keywords>
<keywords scheme="MESH" qualifier="mortality" xml:lang="en"><term>Coronavirus Infections</term>
<term>Cytokine Release Syndrome</term>
<term>Pneumonia, Viral</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Betacoronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="statistics & numerical data" xml:lang="en"><term>Length of Stay</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Coronavirus Infections</term>
<term>Cytokine Release Syndrome</term>
<term>Pneumonia, Viral</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adult</term>
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>COVID-19</term>
<term>Drug Administration Schedule</term>
<term>Drug Combinations</term>
<term>Female</term>
<term>Hospitals, University</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Pandemics</term>
<term>Retrospective Studies</term>
<term>SARS-CoV-2</term>
<term>Severity of Illness Index</term>
<term>Survival Analysis</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Coronavirus disease 2019 (COVID-19) leads to inflammatory cytokine release, which can downregulate the expression of metabolizing enzymes. This cascade affects drug concentrations in the plasma. We investigated the association between lopinavir (LPV) and hydroxychloroquine (HCQ) plasma concentrations and the levels of the acute-phase inflammation marker C-reactive protein (CRP). LPV plasma concentrations in 92 patients hospitalized at our institution were prospectively collected. Lopinavir-ritonavir was administered every 12 hours, 800/200 mg on day 1 and 400/100 mg on day 2 until day 5 or 7. HCQ was given at 800 mg, followed by 400 mg after 6, 24, and 48 h. Hematological, liver, kidney, and inflammation laboratory values were analyzed on the day of drug level determination. The median age of study participants was 59 (range, 24 to 85) years, and 71% were male. The median durations from symptom onset to hospitalization and treatment initiation were 7 days (interquartile range [IQR], 4 to 10) and 8 days (IQR, 5 to 10), respectively. The median LPV trough concentration on day 3 of treatment was 26.5 μg/ml (IQR, 18.9 to 31.5). LPV plasma concentrations positively correlated with CRP values (<i>r</i>
 = 0.37, <i>P</i>
 < 0.001) and were significantly lower when tocilizumab was preadministered. No correlation was found between HCQ concentrations and CRP values. High LPV plasma concentrations were observed in COVID-19 patients. The ratio of calculated unbound drug fraction to published SARS-CoV-2 50% effective concentrations (EC<sub>50</sub>
) indicated insufficient LPV concentrations in the lung. CRP values significantly correlated with LPV but not HCQ plasma concentrations, implying inhibition of cytochrome P450 3A4 (CYP3A4) metabolism by inflammation.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">32641296</PMID>
<DateCompleted><Year>2020</Year>
<Month>09</Month>
<Day>02</Day>
</DateCompleted>
<DateRevised><Year>2020</Year>
<Month>12</Month>
<Day>18</Day>
</DateRevised>
<Article PubModel="Electronic-Print"><Journal><ISSN IssnType="Electronic">1098-6596</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>64</Volume>
<Issue>9</Issue>
<PubDate><Year>2020</Year>
<Month>08</Month>
<Day>20</Day>
</PubDate>
</JournalIssue>
<Title>Antimicrobial agents and chemotherapy</Title>
<ISOAbbreviation>Antimicrob Agents Chemother</ISOAbbreviation>
</Journal>
<ArticleTitle>Effect of Systemic Inflammatory Response to SARS-CoV-2 on Lopinavir and Hydroxychloroquine Plasma Concentrations.</ArticleTitle>
<ELocationID EIdType="pii" ValidYN="Y">e01177-20</ELocationID>
<ELocationID EIdType="doi" ValidYN="Y">10.1128/AAC.01177-20</ELocationID>
<Abstract><AbstractText>Coronavirus disease 2019 (COVID-19) leads to inflammatory cytokine release, which can downregulate the expression of metabolizing enzymes. This cascade affects drug concentrations in the plasma. We investigated the association between lopinavir (LPV) and hydroxychloroquine (HCQ) plasma concentrations and the levels of the acute-phase inflammation marker C-reactive protein (CRP). LPV plasma concentrations in 92 patients hospitalized at our institution were prospectively collected. Lopinavir-ritonavir was administered every 12 hours, 800/200 mg on day 1 and 400/100 mg on day 2 until day 5 or 7. HCQ was given at 800 mg, followed by 400 mg after 6, 24, and 48 h. Hematological, liver, kidney, and inflammation laboratory values were analyzed on the day of drug level determination. The median age of study participants was 59 (range, 24 to 85) years, and 71% were male. The median durations from symptom onset to hospitalization and treatment initiation were 7 days (interquartile range [IQR], 4 to 10) and 8 days (IQR, 5 to 10), respectively. The median LPV trough concentration on day 3 of treatment was 26.5 μg/ml (IQR, 18.9 to 31.5). LPV plasma concentrations positively correlated with CRP values (<i>r</i>
 = 0.37, <i>P</i>
 < 0.001) and were significantly lower when tocilizumab was preadministered. No correlation was found between HCQ concentrations and CRP values. High LPV plasma concentrations were observed in COVID-19 patients. The ratio of calculated unbound drug fraction to published SARS-CoV-2 50% effective concentrations (EC<sub>50</sub>
) indicated insufficient LPV concentrations in the lung. CRP values significantly correlated with LPV but not HCQ plasma concentrations, implying inhibition of cytochrome P450 3A4 (CYP3A4) metabolism by inflammation.</AbstractText>
<CopyrightInformation>Copyright © 2020 American Society for Microbiology.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Marzolini</LastName>
<ForeName>Catia</ForeName>
<Initials>C</Initials>
<Identifier Source="ORCID">0000-0002-2312-7050</Identifier>
<AffiliationInfo><Affiliation>Division of Infectious Diseases & Hospital Hygiene, University Hospital Basel and University of Basel, Basel, Switzerland catia.marzolini@usb.ch parham.sendi@usb.ch.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Stader</LastName>
<ForeName>Felix</ForeName>
<Initials>F</Initials>
<AffiliationInfo><Affiliation>Division of Infectious Diseases & Hospital Hygiene, University Hospital Basel and University of Basel, Basel, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Stoeckle</LastName>
<ForeName>Marcel</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Division of Infectious Diseases & Hospital Hygiene, University Hospital Basel and University of Basel, Basel, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Franzeck</LastName>
<ForeName>Fabian</ForeName>
<Initials>F</Initials>
<AffiliationInfo><Affiliation>Division of Infectious Diseases & Hospital Hygiene, University Hospital Basel and University of Basel, Basel, Switzerland.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Research and Analysis Services, University Hospital Basel and University of Basel, Basel, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Egli</LastName>
<ForeName>Adrian</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Division of Clinical Bacteriology and Mycology, University Hospital Basel, Basel, Switzerland.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Applied Microbiology Research, Department of Biomedicine, University of Basel, Basel, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bassetti</LastName>
<ForeName>Stefano</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Division of Internal Medicine and Department of Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Hollinger</LastName>
<ForeName>Alexa</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Intensive Care Unit, University Hospital Basel, Basel, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Osthoff</LastName>
<ForeName>Michael</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Division of Internal Medicine and Department of Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Weisser</LastName>
<ForeName>Maja</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Division of Infectious Diseases & Hospital Hygiene, University Hospital Basel and University of Basel, Basel, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Gebhard</LastName>
<ForeName>Caroline E</ForeName>
<Initials>CE</Initials>
<AffiliationInfo><Affiliation>Intensive Care Unit, University Hospital Basel, Basel, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Baettig</LastName>
<ForeName>Veronika</ForeName>
<Initials>V</Initials>
<AffiliationInfo><Affiliation>Division of Infectious Diseases & Hospital Hygiene, University Hospital Basel and University of Basel, Basel, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Geenen</LastName>
<ForeName>Julia</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Division of Internal Medicine and Department of Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Khanna</LastName>
<ForeName>Nina</ForeName>
<Initials>N</Initials>
<AffiliationInfo><Affiliation>Division of Infectious Diseases & Hospital Hygiene, University Hospital Basel and University of Basel, Basel, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Tschudin-Sutter</LastName>
<ForeName>Sarah</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Division of Infectious Diseases & Hospital Hygiene, University Hospital Basel and University of Basel, Basel, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Mueller</LastName>
<ForeName>Daniel</ForeName>
<Initials>D</Initials>
<AffiliationInfo><Affiliation>Institute of Clinical Chemistry, University Hospital Zurich, Zurich, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Hirsch</LastName>
<ForeName>Hans H</ForeName>
<Initials>HH</Initials>
<AffiliationInfo><Affiliation>Division of Infectious Diseases & Hospital Hygiene, University Hospital Basel and University of Basel, Basel, Switzerland.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Transplantation & Clinical Virology, Department of Biomedicine, University of Basel, Basel, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y" EqualContrib="Y"><LastName>Battegay</LastName>
<ForeName>Manuel</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Division of Infectious Diseases & Hospital Hygiene, University Hospital Basel and University of Basel, Basel, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y" EqualContrib="Y"><LastName>Sendi</LastName>
<ForeName>Parham</ForeName>
<Initials>P</Initials>
<AffiliationInfo><Affiliation>Division of Infectious Diseases & Hospital Hygiene, University Hospital Basel and University of Basel, Basel, Switzerland catia.marzolini@usb.ch parham.sendi@usb.ch.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Institute for Infectious Diseases, University of Bern, Bern, Switzerland.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2020</Year>
<Month>08</Month>
<Day>20</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>Antimicrob Agents Chemother</MedlineTA>
<NlmUniqueID>0315061</NlmUniqueID>
<ISSNLinking>0066-4804</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D061067">Antibodies, Monoclonal, Humanized</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000998">Antiviral Agents</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D015415">Biomarkers</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D004338">Drug Combinations</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C558899">lopinavir-ritonavir drug combination</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>2494G1JF75</RegistryNumber>
<NameOfSubstance UI="D061466">Lopinavir</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>4QWG6N8QKH</RegistryNumber>
<NameOfSubstance UI="D006886">Hydroxychloroquine</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>9007-41-4</RegistryNumber>
<NameOfSubstance UI="D002097">C-Reactive Protein</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>I031V2H011</RegistryNumber>
<NameOfSubstance UI="C502936">tocilizumab</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>O3J8G9O825</RegistryNumber>
<NameOfSubstance UI="D019438">Ritonavir</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000369" MajorTopicYN="N">Aged, 80 and over</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D061067" MajorTopicYN="N">Antibodies, Monoclonal, Humanized</DescriptorName>
<QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000998" MajorTopicYN="N">Antiviral Agents</DescriptorName>
<QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName>
<QualifierName UI="Q000493" MajorTopicYN="Y">pharmacokinetics</QualifierName>
<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000073640" MajorTopicYN="N">Betacoronavirus</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000472" MajorTopicYN="N">pathogenicity</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015415" MajorTopicYN="N">Biomarkers</DescriptorName>
<QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D002097" MajorTopicYN="N">C-Reactive Protein</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000086382" MajorTopicYN="N">COVID-19</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D018352" MajorTopicYN="N">Coronavirus Infections</DescriptorName>
<QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000401" MajorTopicYN="N">mortality</QualifierName>
<QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000080424" MajorTopicYN="N">Cytokine Release Syndrome</DescriptorName>
<QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000401" MajorTopicYN="N">mortality</QualifierName>
<QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004334" MajorTopicYN="N">Drug Administration Schedule</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004338" MajorTopicYN="N">Drug Combinations</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006785" MajorTopicYN="N">Hospitals, University</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006886" MajorTopicYN="N">Hydroxychloroquine</DescriptorName>
<QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName>
<QualifierName UI="Q000493" MajorTopicYN="Y">pharmacokinetics</QualifierName>
<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D007902" MajorTopicYN="N">Length of Stay</DescriptorName>
<QualifierName UI="Q000706" MajorTopicYN="N">statistics & numerical data</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D061466" MajorTopicYN="N">Lopinavir</DescriptorName>
<QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName>
<QualifierName UI="Q000493" MajorTopicYN="Y">pharmacokinetics</QualifierName>
<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D058873" MajorTopicYN="N">Pandemics</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D011024" MajorTopicYN="N">Pneumonia, Viral</DescriptorName>
<QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000401" MajorTopicYN="N">mortality</QualifierName>
<QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D012189" MajorTopicYN="N">Retrospective Studies</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D019438" MajorTopicYN="N">Ritonavir</DescriptorName>
<QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName>
<QualifierName UI="Q000493" MajorTopicYN="Y">pharmacokinetics</QualifierName>
<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000086402" MajorTopicYN="N">SARS-CoV-2</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D012720" MajorTopicYN="N">Severity of Illness Index</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D016019" MajorTopicYN="N">Survival Analysis</DescriptorName>
</MeshHeading>
</MeshHeadingList>
<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">COVID-19</Keyword>
<Keyword MajorTopicYN="Y">hydroxychloroquine</Keyword>
<Keyword MajorTopicYN="Y">inflammation</Keyword>
<Keyword MajorTopicYN="Y">levels</Keyword>
<Keyword MajorTopicYN="Y">lopinavir-ritonavir</Keyword>
</KeywordList>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year>
<Month>06</Month>
<Day>09</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted"><Year>2020</Year>
<Month>07</Month>
<Day>06</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed"><Year>2020</Year>
<Month>7</Month>
<Day>10</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline"><Year>2020</Year>
<Month>9</Month>
<Day>4</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez"><Year>2020</Year>
<Month>7</Month>
<Day>10</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>epublish</PublicationStatus>
<ArticleIdList><ArticleId IdType="pubmed">32641296</ArticleId>
<ArticleId IdType="pii">AAC.01177-20</ArticleId>
<ArticleId IdType="doi">10.1128/AAC.01177-20</ArticleId>
<ArticleId IdType="pmc">PMC7449226</ArticleId>
</ArticleIdList>
<ReferenceList><Reference><Citation>AIDS. 2003 Jul 25;17(11):1710-1</Citation>
<ArticleIdList><ArticleId IdType="pubmed">12853760</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Br J Clin Pharmacol. 2013 Sep;76(3):455-66</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23305158</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Infect Dis Ther. 2020 Sep;9(3):435-449</Citation>
<ArticleIdList><ArticleId IdType="pubmed">32462545</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Clin Pharmacokinet. 2020 Mar;59(3):383-401</Citation>
<ArticleIdList><ArticleId IdType="pubmed">31583609</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Clin Infect Dis. 2020 May 21;:</Citation>
<ArticleIdList><ArticleId IdType="pubmed">32435791</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Clin Drug Investig. 2020 Jun;40(6):511-518</Citation>
<ArticleIdList><ArticleId IdType="pubmed">32337664</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Br J Clin Pharmacol. 2018 Sep;84(9):1980-1988</Citation>
<ArticleIdList><ArticleId IdType="pubmed">29744898</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>JAMA. 2020 Apr 7;323(13):1239-1242</Citation>
<ArticleIdList><ArticleId IdType="pubmed">32091533</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Psychopharmacology (Berl). 2016 May;233(9):1695-705</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26032842</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Antiviral Res. 2020 Jun;178:104786</Citation>
<ArticleIdList><ArticleId IdType="pubmed">32251767</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>N Engl J Med. 2020 May 7;382(19):1787-1799</Citation>
<ArticleIdList><ArticleId IdType="pubmed">32187464</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Clin Endocrinol Metab. 2000 Mar;85(3):1331-3</Citation>
<ArticleIdList><ArticleId IdType="pubmed">10720086</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>AIDS. 2008 May 11;22(8):931-5</Citation>
<ArticleIdList><ArticleId IdType="pubmed">18453852</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Oncologist. 2018 Aug;23(8):943-947</Citation>
<ArticleIdList><ArticleId IdType="pubmed">29622697</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Clin Pharmacol. 2007 Aug;47(8):970-7</Citation>
<ArticleIdList><ArticleId IdType="pubmed">17615254</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Eur J Clin Pharmacol. 2013 Oct;69(10):1795-800</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23748748</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Biol Chem. 2005 Mar 11;280(10):9610-7</Citation>
<ArticleIdList><ArticleId IdType="pubmed">15632119</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>N Engl J Med. 2020 Aug 6;383(6):517-525</Citation>
<ArticleIdList><ArticleId IdType="pubmed">32492293</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Mod Rheumatol. 2013 Sep;23(5):977-85</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23099471</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Drugs. 2010 Oct 1;70(14):1885-915</Citation>
<ArticleIdList><ArticleId IdType="pubmed">20836579</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Antimicrob Chemother. 2020 Sep 1;75(9):2704-2706</Citation>
<ArticleIdList><ArticleId IdType="pubmed">32407513</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Thromb Haemost. 2020 Jun;18(6):1320-1323</Citation>
<ArticleIdList><ArticleId IdType="pubmed">32329231</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Infect Dis. 2004 Jan 15;189(2):265-72</Citation>
<ArticleIdList><ArticleId IdType="pubmed">14722892</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Expert Opin Drug Metab Toxicol. 2005 Dec;1(4):629-40</Citation>
<ArticleIdList><ArticleId IdType="pubmed">16863429</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Ann Intern Med. 2020 May 12;:</Citation>
<ArticleIdList><ArticleId IdType="pubmed">32422065</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Clin Pharmacol Ther. 2009 Apr;85(4):434-8</Citation>
<ArticleIdList><ArticleId IdType="pubmed">19212314</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Drug Metab Dispos. 2011 Aug;39(8):1415-22</Citation>
<ArticleIdList><ArticleId IdType="pubmed">21555507</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Open Forum Infect Dis. 2015 Jul 03;2(3):ofv098</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26258155</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Drug Metab Dispos. 2008 Feb;36(2):205-16</Citation>
<ArticleIdList><ArticleId IdType="pubmed">18218849</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Int AIDS Soc. 2020 Apr;23(4):e25489</Citation>
<ArticleIdList><ArticleId IdType="pubmed">32293807</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Antimicrob Chemother. 2020 Jun 17;:</Citation>
<ArticleIdList><ArticleId IdType="pubmed">32556272</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Ther Drug Monit. 2016 Apr;38(2):259-67</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26587870</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Antimicrob Chemother. 2020 Sep 1;75(9):2702-2704</Citation>
<ArticleIdList><ArticleId IdType="pubmed">32443151</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Science. 2020 Apr 24;368(6489):409-412</Citation>
<ArticleIdList><ArticleId IdType="pubmed">32198291</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Nat Commun. 2020 Jan 10;11(1):222</Citation>
<ArticleIdList><ArticleId IdType="pubmed">31924756</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Pharm Sci. 2016 Feb;105(2):884-890</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26429523</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>N Engl J Med. 2020 Jun 18;382(25):2411-2418</Citation>
<ArticleIdList><ArticleId IdType="pubmed">32379955</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Clin Infect Dis. 2020 May 11;:</Citation>
<ArticleIdList><ArticleId IdType="pubmed">32392332</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Int J Antimicrob Agents. 2020 Aug;56(2):106028</Citation>
<ArticleIdList><ArticleId IdType="pubmed">32450198</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Acquir Immune Defic Syndr. 2015 Dec 15;70(5):510-4</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26230332</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
</PubmedData>
</pubmed>
</record>

Pour manipuler ce document sous Unix (Dilib)

EXPLOR_STEP=$WICRI_ROOT/Sante/explor/CovidChloroV1/Data/Main/Corpus

HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001200 | SxmlIndent | more

HfdSelect -h $EXPLOR_AREA/Data/Main/Corpus/biblio.hfd -nk 001200 | SxmlIndent | more

Pour mettre un lien sur cette page dans le réseau Wicri

{{Explor lien
   |wiki=    Sante
   |area=    CovidChloroV1
   |flux=    Main
   |étape=   Corpus
   |type=    RBID
   |clé=     pubmed:32641296
   |texte=   Effect of Systemic Inflammatory Response to SARS-CoV-2 on Lopinavir and Hydroxychloroquine Plasma Concentrations.
}}

Pour générer des pages wiki

HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Corpus/RBID.i   -Sk "pubmed:32641296" \
       | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Corpus/biblio.hfd   \
       | NlmPubMed2Wicri -a CovidChloroV1

This area was generated with Dilib version V0.6.38.
Data generation: Sat May 22 17:02:32 2021. Site generation: Sat May 22 17:06:52 2021

	Serveur d'exploration COVID et hydrochloroquine
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.

Serveur d'exploration COVID et hydrochloroquine

Effect of Systemic Inflammatory Response to SARS-CoV-2 on Lopinavir and Hydroxychloroquine Plasma Concentrations.

Effect of Systemic Inflammatory Response to SARS-CoV-2 on Lopinavir and Hydroxychloroquine Plasma Concentrations.

Source :

English descriptors

Abstract

Links to Exploration step

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri

Pour générer des pages wiki