A Pharmacokinetics-Informed Approach to Navigating Hydroxychloroquine Shortages in Patients With Rheumatic Disease During the COVID-19 Pandemic.
Identifieur interne : 001042 ( Main/Corpus ); précédent : 001041; suivant : 001043A Pharmacokinetics-Informed Approach to Navigating Hydroxychloroquine Shortages in Patients With Rheumatic Disease During the COVID-19 Pandemic.
Auteurs : Marc H. Scheetz ; Maximilian F. Konig ; Philip C. Robinson ; Jeffrey A. Sparks ; Alfred H J. KimSource :
- ACR open rheumatology [ 2578-5745 ] ; 2020.
Abstract
OBJECTIVE
The recent hydroxychloroquine (HCQ) shortage due to use in coronavirus disease 2019 (COVID-19) has forced some rheumatic disease patients to choose between continuing their current dose of HCQ but exhaust their supply early or ration it in order to prolong its use. Blood HCQ concentrations are directly correlated with disease activity in rheumatic diseases such as systemic lupus erythematosus. We sought to model how changes in HCQ dosage will best maintain sufficient blood HCQ concentrations for the longest period of time in order to avoid potential future flares.
METHODS
A one-compartment pharmacokinetic model was used to predict mean blood HCQ concentrations. Monte Carlo simulations with 10-fold inflated model parameter variance was utilized to assess the impact of variability.
RESULTS
Maintenance of 400 mg/d resulted in mean therapeutic whole-blood HCQ concentrations that exceeded 700 ng/ml for 10.5 days, whereas HCQ rationing by reducing the dose by half resulted in the mean concentration remaining above 700 ng/ml for 2.4 days (net gain = 8 days). Variability analysis demonstrates that results may differ at the individual level, dependent on baseline blood HCQ concentrations.
CONCLUSION
Although mean blood concentrations exceed 700 ng/ml for a longer time if patients maintain their full dose of HCQ, more information is needed to fully understand the elimination of HCQ at the patient level, particularly the contribution of tissue stores of HCQ transiting back into the blood.
DOI: 10.1002/acr2.11164
PubMed: 32725866
PubMed Central: PMC7437131
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A Pharmacokinetics-Informed Approach to Navigating Hydroxychloroquine Shortages in Patients With Rheumatic Disease During the COVID-19 Pandemic.</title><author><name sortKey="Scheetz, Marc H" sort="Scheetz, Marc H" uniqKey="Scheetz M" first="Marc H" last="Scheetz">Marc H. Scheetz</name><affiliation><nlm:affiliation>Midwestern University and Midwestern University Pharmacometrics Center of Excellence, Downers Grove, Illinois, and Northwestern Memorial Hospital, Chicago, Illinois.</nlm:affiliation></affiliation></author><author><name sortKey="Konig, Maximilian F" sort="Konig, Maximilian F" uniqKey="Konig M" first="Maximilian F" last="Konig">Maximilian F. Konig</name><affiliation><nlm:affiliation>Johns Hopkins University School of Medicine, Baltimore, Maryland.</nlm:affiliation></affiliation></author><author><name sortKey="Robinson, Philip C" sort="Robinson, Philip C" uniqKey="Robinson P" first="Philip C" last="Robinson">Philip C. Robinson</name><affiliation><nlm:affiliation>University of Queensland Faculty of Medicine, Brisbane, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Sparks, Jeffrey A" sort="Sparks, Jeffrey A" uniqKey="Sparks J" first="Jeffrey A" last="Sparks">Jeffrey A. Sparks</name><affiliation><nlm:affiliation>Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.</nlm:affiliation></affiliation></author><author><name sortKey="Kim, Alfred H J" sort="Kim, Alfred H J" uniqKey="Kim A" first="Alfred H J" last="Kim">Alfred H J. Kim</name><affiliation><nlm:affiliation>Washington University School of Medicine, Saint Louis, Missouri.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32725866</idno><idno type="pmid">32725866</idno><idno type="doi">10.1002/acr2.11164</idno><idno type="pmc">PMC7437131</idno><idno type="wicri:Area/Main/Corpus">001042</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">001042</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">A Pharmacokinetics-Informed Approach to Navigating Hydroxychloroquine Shortages in Patients With Rheumatic Disease During the COVID-19 Pandemic.</title><author><name sortKey="Scheetz, Marc H" sort="Scheetz, Marc H" uniqKey="Scheetz M" first="Marc H" last="Scheetz">Marc H. Scheetz</name><affiliation><nlm:affiliation>Midwestern University and Midwestern University Pharmacometrics Center of Excellence, Downers Grove, Illinois, and Northwestern Memorial Hospital, Chicago, Illinois.</nlm:affiliation></affiliation></author><author><name sortKey="Konig, Maximilian F" sort="Konig, Maximilian F" uniqKey="Konig M" first="Maximilian F" last="Konig">Maximilian F. Konig</name><affiliation><nlm:affiliation>Johns Hopkins University School of Medicine, Baltimore, Maryland.</nlm:affiliation></affiliation></author><author><name sortKey="Robinson, Philip C" sort="Robinson, Philip C" uniqKey="Robinson P" first="Philip C" last="Robinson">Philip C. Robinson</name><affiliation><nlm:affiliation>University of Queensland Faculty of Medicine, Brisbane, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Sparks, Jeffrey A" sort="Sparks, Jeffrey A" uniqKey="Sparks J" first="Jeffrey A" last="Sparks">Jeffrey A. Sparks</name><affiliation><nlm:affiliation>Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.</nlm:affiliation></affiliation></author><author><name sortKey="Kim, Alfred H J" sort="Kim, Alfred H J" uniqKey="Kim A" first="Alfred H J" last="Kim">Alfred H J. Kim</name><affiliation><nlm:affiliation>Washington University School of Medicine, Saint Louis, Missouri.</nlm:affiliation></affiliation></author></analytic><series><title level="j">ACR open rheumatology</title><idno type="eISSN">2578-5745</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><b>OBJECTIVE</b></p><p>The recent hydroxychloroquine (HCQ) shortage due to use in coronavirus disease 2019 (COVID-19) has forced some rheumatic disease patients to choose between continuing their current dose of HCQ but exhaust their supply early or ration it in order to prolong its use. Blood HCQ concentrations are directly correlated with disease activity in rheumatic diseases such as systemic lupus erythematosus. We sought to model how changes in HCQ dosage will best maintain sufficient blood HCQ concentrations for the longest period of time in order to avoid potential future flares.</p></div><div type="abstract" xml:lang="en"><p><b>METHODS</b></p><p>A one-compartment pharmacokinetic model was used to predict mean blood HCQ concentrations. Monte Carlo simulations with 10-fold inflated model parameter variance was utilized to assess the impact of variability.</p></div><div type="abstract" xml:lang="en"><p><b>RESULTS</b></p><p>Maintenance of 400 mg/d resulted in mean therapeutic whole-blood HCQ concentrations that exceeded 700 ng/ml for 10.5 days, whereas HCQ rationing by reducing the dose by half resulted in the mean concentration remaining above 700 ng/ml for 2.4 days (net gain = 8 days). Variability analysis demonstrates that results may differ at the individual level, dependent on baseline blood HCQ concentrations.</p></div><div type="abstract" xml:lang="en"><p><b>CONCLUSION</b></p><p>Although mean blood concentrations exceed 700 ng/ml for a longer time if patients maintain their full dose of HCQ, more information is needed to fully understand the elimination of HCQ at the patient level, particularly the contribution of tissue stores of HCQ transiting back into the blood.</p></div></front></TEI><pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">32725866</PMID><DateRevised><Year>2021</Year><Month>01</Month><Day>10</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">2578-5745</ISSN><JournalIssue CitedMedium="Internet"><Volume>2</Volume><Issue>8</Issue><PubDate><Year>2020</Year><Month>Aug</Month></PubDate></JournalIssue><Title>ACR open rheumatology</Title><ISOAbbreviation>ACR Open Rheumatol</ISOAbbreviation></Journal><ArticleTitle>A Pharmacokinetics-Informed Approach to Navigating Hydroxychloroquine Shortages in Patients With Rheumatic Disease During the COVID-19 Pandemic.</ArticleTitle><Pagination><MedlinePgn>491-495</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1002/acr2.11164</ELocationID><Abstract><AbstractText Label="OBJECTIVE" NlmCategory="OBJECTIVE">The recent hydroxychloroquine (HCQ) shortage due to use in coronavirus disease 2019 (COVID-19) has forced some rheumatic disease patients to choose between continuing their current dose of HCQ but exhaust their supply early or ration it in order to prolong its use. Blood HCQ concentrations are directly correlated with disease activity in rheumatic diseases such as systemic lupus erythematosus. We sought to model how changes in HCQ dosage will best maintain sufficient blood HCQ concentrations for the longest period of time in order to avoid potential future flares.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">A one-compartment pharmacokinetic model was used to predict mean blood HCQ concentrations. Monte Carlo simulations with 10-fold inflated model parameter variance was utilized to assess the impact of variability.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">Maintenance of 400 mg/d resulted in mean therapeutic whole-blood HCQ concentrations that exceeded 700 ng/ml for 10.5 days, whereas HCQ rationing by reducing the dose by half resulted in the mean concentration remaining above 700 ng/ml for 2.4 days (net gain = 8 days). Variability analysis demonstrates that results may differ at the individual level, dependent on baseline blood HCQ concentrations.</AbstractText><AbstractText Label="CONCLUSION" NlmCategory="CONCLUSIONS">Although mean blood concentrations exceed 700 ng/ml for a longer time if patients maintain their full dose of HCQ, more information is needed to fully understand the elimination of HCQ at the patient level, particularly the contribution of tissue stores of HCQ transiting back into the blood.</AbstractText><CopyrightInformation>© 2020 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Scheetz</LastName><ForeName>Marc H</ForeName><Initials>MH</Initials><AffiliationInfo><Affiliation>Midwestern University and Midwestern University Pharmacometrics Center of Excellence, Downers Grove, Illinois, and Northwestern Memorial Hospital, Chicago, Illinois.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Konig</LastName><ForeName>Maximilian F</ForeName><Initials>MF</Initials><Identifier Source="ORCID">https://orcid.org/0000-0001-5045-5255</Identifier><AffiliationInfo><Affiliation>Johns Hopkins University School of Medicine, Baltimore, Maryland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Robinson</LastName><ForeName>Philip C</ForeName><Initials>PC</Initials><Identifier Source="ORCID">https://orcid.org/0000-0002-3156-3418</Identifier><AffiliationInfo><Affiliation>University of Queensland Faculty of Medicine, Brisbane, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sparks</LastName><ForeName>Jeffrey A</ForeName><Initials>JA</Initials><Identifier Source="ORCID">https://orcid.org/0000-0002-5556-4618</Identifier><AffiliationInfo><Affiliation>Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kim</LastName><ForeName>Alfred H J</ForeName><Initials>AHJ</Initials><Identifier Source="ORCID">https://orcid.org/0000-0003-4074-0516</Identifier><AffiliationInfo><Affiliation>Washington University School of Medicine, Saint Louis, Missouri.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01AI119446</GrantID><Acronym>AR</Acronym><Agency>NIAMS NIH 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