Recommendations for Dosing of Repurposed COVID-19 Medications in Patients with Renal and Hepatic Impairment.
Identifieur interne : 000643 ( Main/Corpus ); précédent : 000642; suivant : 000644Recommendations for Dosing of Repurposed COVID-19 Medications in Patients with Renal and Hepatic Impairment.
Auteurs : Fiona Marra ; Elise J. Smolders ; Omar El-Sherif ; Alison Boyle ; Katherine Davidson ; Andrew J. Sommerville ; Catia Marzolini ; Marco Siccardi ; David Burger ; Sara Gibbons ; Saye Khoo ; David BackSource :
- Drugs in R&D [ 1179-6901 ] ; 2021.
English descriptors
- KwdEn :
- Adenosine Monophosphate (administration & dosage), Adenosine Monophosphate (analogs & derivatives), Alanine (administration & dosage), Alanine (analogs & derivatives), Antiviral Agents (administration & dosage), COVID-19 (diagnosis), COVID-19 (drug therapy), COVID-19 (epidemiology), Clinical Trials as Topic (methods), Dexamethasone (administration & dosage), Dose-Response Relationship, Drug (MeSH), Drug Repositioning (methods), Humans (MeSH), Hydroxychloroquine (administration & dosage), Kidney Diseases (diagnosis), Kidney Diseases (drug therapy), Kidney Diseases (epidemiology), Liver Diseases (diagnosis), Liver Diseases (drug therapy), Liver Diseases (epidemiology).
- MESH :
- chemical , administration & dosage : Adenosine Monophosphate, Alanine, Antiviral Agents, Dexamethasone, Hydroxychloroquine.
- chemical , analogs & derivatives : Adenosine Monophosphate, Alanine.
- diagnosis : COVID-19, Kidney Diseases, Liver Diseases.
- drug therapy : COVID-19, Kidney Diseases, Liver Diseases.
- epidemiology : COVID-19, Kidney Diseases, Liver Diseases.
- methods : Clinical Trials as Topic, Drug Repositioning.
- Dose-Response Relationship, Drug, Humans.
Abstract
INTRODUCTION
In December 2019, an outbreak of a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began, resulting in a number of antivirals and immune modulators being repurposed to treat the associated coronavirus disease 2019 (COVID-19). Many patients requiring treatment for COVID-19 may have either pre-existing renal or hepatic disease or experience acute renal/hepatic injury as a result of the acute infection. Altered renal or hepatic function can significantly affect drug concentrations of medications due to impaired drug metabolism and excretion, resulting in toxicity or reduced efficacy. The aim of this paper is to review the pharmacokinetics and available study data for the experimental COVID-19 therapies in patients with any degree of renal or hepatic impairment to make recommendations for dosing.
METHODS
COVID-19 agents included in these recommendations were listed as primaries on the University of Liverpool COVID-19 drug interaction website ( www.covid19-druginteractions.org ), initially identified from Clinicialtrials.gov and ChicCTR.org.cn. A literature search was performed using PubMed and EMBASE as well as product licences and pharmacokinetic databases.
FINDINGS
Remdesivir, dexamethasone, azithromycin, favipiravir, lopinavir/ritonavir, atazanavir, hydroxychloroquine, interferon beta, ribavirin, tocilizumab, anakinra and sarilumab were identified as experimental drugs being used in COVID-19 trials as of November 2020. Limited study data was found for these drugs in patients with renal or hepatic impairment for COVID-19 or other indications. Recommendations were made based on available data, consideration of pharmacokinetic properties (including variability), the dosing and anticipated treatment duration of each regimen in COVID-19 and known toxicities.
CONCLUSION
Dosing of drugs used to treat COVID-19 in patients with renal or hepatic impairment is complex. These recommendations were produced to provide guidance to clinicians worldwide who are treating patients with COVID-19, many of whom will have some degree of acute or chronic renal or hepatic impairment.
DOI: 10.1007/s40268-020-00333-0
PubMed: 33336316
PubMed Central: PMC7745756
Links to Exploration step
pubmed:33336316Le document en format XML
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Smolders</name><affiliation><nlm:affiliation>Department of Pharmacy, Radboud Institute for Health Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Department of Pharmacy, Isala Hospital, Zwolle, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="El Sherif, Omar" sort="El Sherif, Omar" uniqKey="El Sherif O" first="Omar" last="El-Sherif">Omar El-Sherif</name><affiliation><nlm:affiliation>Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Boyle, Alison" sort="Boyle, Alison" uniqKey="Boyle A" first="Alison" last="Boyle">Alison Boyle</name><affiliation><nlm:affiliation>Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Department of Pharmacy, NHS Greater Glasgow and Clyde, Glasgow, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Davidson, Katherine" sort="Davidson, Katherine" uniqKey="Davidson K" first="Katherine" last="Davidson">Katherine Davidson</name><affiliation><nlm:affiliation>Department of Pharmacy, NHS Lothian, Edinburgh, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Sommerville, Andrew J" sort="Sommerville, Andrew J" uniqKey="Sommerville A" first="Andrew J" last="Sommerville">Andrew J. 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Smolders</name><affiliation><nlm:affiliation>Department of Pharmacy, Radboud Institute for Health Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Department of Pharmacy, Isala Hospital, Zwolle, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="El Sherif, Omar" sort="El Sherif, Omar" uniqKey="El Sherif O" first="Omar" last="El-Sherif">Omar El-Sherif</name><affiliation><nlm:affiliation>Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Boyle, Alison" sort="Boyle, Alison" uniqKey="Boyle A" first="Alison" last="Boyle">Alison Boyle</name><affiliation><nlm:affiliation>Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Department of Pharmacy, NHS Greater Glasgow and Clyde, Glasgow, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Davidson, Katherine" sort="Davidson, Katherine" uniqKey="Davidson K" first="Katherine" last="Davidson">Katherine Davidson</name><affiliation><nlm:affiliation>Department of Pharmacy, NHS Lothian, Edinburgh, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Sommerville, Andrew J" sort="Sommerville, Andrew J" uniqKey="Sommerville A" first="Andrew J" last="Sommerville">Andrew J. Sommerville</name><affiliation><nlm:affiliation>Department of Pharmacy, NHS Greater Glasgow and Clyde, Glasgow, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Marzolini, Catia" sort="Marzolini, Catia" uniqKey="Marzolini C" first="Catia" last="Marzolini">Catia Marzolini</name><affiliation><nlm:affiliation>Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Division of Infectious Diseases and Hospital Epidemiology, Departments of Medicine and Clinical Research, University Hospital of Basel, Basel, Switzerland.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>University of Basel, Basel, Switzerland.</nlm:affiliation></affiliation></author><author><name sortKey="Siccardi, Marco" sort="Siccardi, Marco" uniqKey="Siccardi M" first="Marco" last="Siccardi">Marco Siccardi</name><affiliation><nlm:affiliation>Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Burger, David" sort="Burger, David" uniqKey="Burger D" first="David" last="Burger">David Burger</name><affiliation><nlm:affiliation>Department of Pharmacy, Radboud Institute for Health Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Gibbons, Sara" sort="Gibbons, Sara" uniqKey="Gibbons S" first="Sara" last="Gibbons">Sara Gibbons</name><affiliation><nlm:affiliation>Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Khoo, Saye" sort="Khoo, Saye" uniqKey="Khoo S" first="Saye" last="Khoo">Saye Khoo</name><affiliation><nlm:affiliation>Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Royal Liverpool University Hospital, Liverpool, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Back, David" sort="Back, David" uniqKey="Back D" first="David" last="Back">David Back</name><affiliation><nlm:affiliation>Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Drugs in R&D</title><idno type="eISSN">1179-6901</idno><imprint><date when="2021" type="published">2021</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adenosine Monophosphate (administration & dosage)</term><term>Adenosine Monophosphate (analogs & derivatives)</term><term>Alanine (administration & dosage)</term><term>Alanine (analogs & derivatives)</term><term>Antiviral Agents (administration & dosage)</term><term>COVID-19 (diagnosis)</term><term>COVID-19 (drug therapy)</term><term>COVID-19 (epidemiology)</term><term>Clinical Trials as Topic (methods)</term><term>Dexamethasone (administration & dosage)</term><term>Dose-Response Relationship, Drug (MeSH)</term><term>Drug Repositioning (methods)</term><term>Humans (MeSH)</term><term>Hydroxychloroquine (administration & dosage)</term><term>Kidney Diseases (diagnosis)</term><term>Kidney Diseases (drug therapy)</term><term>Kidney Diseases (epidemiology)</term><term>Liver Diseases (diagnosis)</term><term>Liver Diseases (drug therapy)</term><term>Liver Diseases (epidemiology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Adenosine Monophosphate</term><term>Alanine</term><term>Antiviral Agents</term><term>Dexamethasone</term><term>Hydroxychloroquine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Adenosine Monophosphate</term><term>Alanine</term></keywords><keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>COVID-19</term><term>Kidney Diseases</term><term>Liver Diseases</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>COVID-19</term><term>Kidney Diseases</term><term>Liver Diseases</term></keywords><keywords scheme="MESH" qualifier="epidemiology" xml:lang="en"><term>COVID-19</term><term>Kidney Diseases</term><term>Liver Diseases</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Clinical Trials as Topic</term><term>Drug Repositioning</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Dose-Response Relationship, Drug</term><term>Humans</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><b>INTRODUCTION</b></p><p>In December 2019, an outbreak of a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began, resulting in a number of antivirals and immune modulators being repurposed to treat the associated coronavirus disease 2019 (COVID-19). Many patients requiring treatment for COVID-19 may have either pre-existing renal or hepatic disease or experience acute renal/hepatic injury as a result of the acute infection. Altered renal or hepatic function can significantly affect drug concentrations of medications due to impaired drug metabolism and excretion, resulting in toxicity or reduced efficacy. The aim of this paper is to review the pharmacokinetics and available study data for the experimental COVID-19 therapies in patients with any degree of renal or hepatic impairment to make recommendations for dosing.</p></div><div type="abstract" xml:lang="en"><p><b>METHODS</b></p><p>COVID-19 agents included in these recommendations were listed as primaries on the University of Liverpool COVID-19 drug interaction website ( www.covid19-druginteractions.org ), initially identified from Clinicialtrials.gov and ChicCTR.org.cn. A literature search was performed using PubMed and EMBASE as well as product licences and pharmacokinetic databases.</p></div><div type="abstract" xml:lang="en"><p><b>FINDINGS</b></p><p>Remdesivir, dexamethasone, azithromycin, favipiravir, lopinavir/ritonavir, atazanavir, hydroxychloroquine, interferon beta, ribavirin, tocilizumab, anakinra and sarilumab were identified as experimental drugs being used in COVID-19 trials as of November 2020. Limited study data was found for these drugs in patients with renal or hepatic impairment for COVID-19 or other indications. Recommendations were made based on available data, consideration of pharmacokinetic properties (including variability), the dosing and anticipated treatment duration of each regimen in COVID-19 and known toxicities.</p></div><div type="abstract" xml:lang="en"><p><b>CONCLUSION</b></p><p>Dosing of drugs used to treat COVID-19 in patients with renal or hepatic impairment is complex. These recommendations were produced to provide guidance to clinicians worldwide who are treating patients with COVID-19, many of whom will have some degree of acute or chronic renal or hepatic impairment.</p></div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">33336316</PMID><DateCompleted><Year>2021</Year><Month>03</Month><Day>15</Day></DateCompleted><DateRevised><Year>2021</Year><Month>03</Month><Day>15</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1179-6901</ISSN><JournalIssue CitedMedium="Internet"><Volume>21</Volume><Issue>1</Issue><PubDate><Year>2021</Year><Month>Mar</Month></PubDate></JournalIssue><Title>Drugs in R&D</Title><ISOAbbreviation>Drugs R D</ISOAbbreviation></Journal><ArticleTitle>Recommendations for Dosing of Repurposed COVID-19 Medications in Patients with Renal and Hepatic Impairment.</ArticleTitle><Pagination><MedlinePgn>9-27</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1007/s40268-020-00333-0</ELocationID><Abstract><AbstractText Label="INTRODUCTION" NlmCategory="BACKGROUND">In December 2019, an outbreak of a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began, resulting in a number of antivirals and immune modulators being repurposed to treat the associated coronavirus disease 2019 (COVID-19). Many patients requiring treatment for COVID-19 may have either pre-existing renal or hepatic disease or experience acute renal/hepatic injury as a result of the acute infection. Altered renal or hepatic function can significantly affect drug concentrations of medications due to impaired drug metabolism and excretion, resulting in toxicity or reduced efficacy. The aim of this paper is to review the pharmacokinetics and available study data for the experimental COVID-19 therapies in patients with any degree of renal or hepatic impairment to make recommendations for dosing.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">COVID-19 agents included in these recommendations were listed as primaries on the University of Liverpool COVID-19 drug interaction website ( www.covid19-druginteractions.org ), initially identified from Clinicialtrials.gov and ChicCTR.org.cn. A literature search was performed using PubMed and EMBASE as well as product licences and pharmacokinetic databases.</AbstractText><AbstractText Label="FINDINGS" NlmCategory="RESULTS">Remdesivir, dexamethasone, azithromycin, favipiravir, lopinavir/ritonavir, atazanavir, hydroxychloroquine, interferon beta, ribavirin, tocilizumab, anakinra and sarilumab were identified as experimental drugs being used in COVID-19 trials as of November 2020. Limited study data was found for these drugs in patients with renal or hepatic impairment for COVID-19 or other indications. Recommendations were made based on available data, consideration of pharmacokinetic properties (including variability), the dosing and anticipated treatment duration of each regimen in COVID-19 and known toxicities.</AbstractText><AbstractText Label="CONCLUSION" NlmCategory="CONCLUSIONS">Dosing of drugs used to treat COVID-19 in patients with renal or hepatic impairment is complex. These recommendations were produced to provide guidance to clinicians worldwide who are treating patients with COVID-19, many of whom will have some degree of acute or chronic renal or hepatic impairment.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y" EqualContrib="Y"><LastName>Marra</LastName><ForeName>Fiona</ForeName><Initials>F</Initials><Identifier Source="ORCID">http://orcid.org/0000-0003-1326-1149</Identifier><AffiliationInfo><Affiliation>Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK. fmarra@liverpool.ac.uk.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Pharmacy, NHS Greater Glasgow and Clyde, Glasgow, UK. fmarra@liverpool.ac.uk.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y" EqualContrib="Y"><LastName>Smolders</LastName><ForeName>Elise J</ForeName><Initials>EJ</Initials><AffiliationInfo><Affiliation>Department of Pharmacy, Radboud Institute for Health Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Pharmacy, Isala Hospital, Zwolle, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>El-Sherif</LastName><ForeName>Omar</ForeName><Initials>O</Initials><AffiliationInfo><Affiliation>Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Boyle</LastName><ForeName>Alison</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Pharmacy, NHS Greater Glasgow and Clyde, Glasgow, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Davidson</LastName><ForeName>Katherine</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Pharmacy, NHS Lothian, Edinburgh, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sommerville</LastName><ForeName>Andrew J</ForeName><Initials>AJ</Initials><AffiliationInfo><Affiliation>Department of Pharmacy, NHS Greater Glasgow and Clyde, Glasgow, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Marzolini</LastName><ForeName>Catia</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Division of Infectious Diseases and Hospital Epidemiology, Departments of Medicine and Clinical Research, University Hospital of Basel, Basel, Switzerland.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>University of Basel, Basel, Switzerland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Siccardi</LastName><ForeName>Marco</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Burger</LastName><ForeName>David</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Department of Pharmacy, Radboud Institute for Health Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gibbons</LastName><ForeName>Sara</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Khoo</LastName><ForeName>Saye</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Royal Liverpool University Hospital, Liverpool, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Back</LastName><ForeName>David</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016454">Review</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>12</Month><Day>17</Day></ArticleDate></Article><MedlineJournalInfo><Country>New Zealand</Country><MedlineTA>Drugs R D</MedlineTA><NlmUniqueID>100883647</NlmUniqueID><ISSNLinking>1174-5886</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000998">Antiviral Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>3QKI37EEHE</RegistryNumber><NameOfSubstance UI="C000606551">remdesivir</NameOfSubstance></Chemical><Chemical><RegistryNumber>415SHH325A</RegistryNumber><NameOfSubstance UI="D000249">Adenosine Monophosphate</NameOfSubstance></Chemical><Chemical><RegistryNumber>4QWG6N8QKH</RegistryNumber><NameOfSubstance UI="D006886">Hydroxychloroquine</NameOfSubstance></Chemical><Chemical><RegistryNumber>7S5I7G3JQL</RegistryNumber><NameOfSubstance UI="D003907">Dexamethasone</NameOfSubstance></Chemical><Chemical><RegistryNumber>OF5P57N2ZX</RegistryNumber><NameOfSubstance UI="D000409">Alanine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000249" MajorTopicYN="N">Adenosine Monophosphate</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000031" MajorTopicYN="N">analogs & derivatives</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000409" MajorTopicYN="N">Alanine</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000031" MajorTopicYN="N">analogs & derivatives</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000998" MajorTopicYN="N">Antiviral Agents</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="Y">administration & dosage</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000086382" MajorTopicYN="N">COVID-19</DescriptorName><QualifierName UI="Q000175" 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