Optimization of hydroxychloroquine dosing scheme based on COVID-19 patients' characteristics: a review of the literature and simulations.
Identifieur interne : 000C13 ( Main/Corpus ); précédent : 000C12; suivant : 000C14Optimization of hydroxychloroquine dosing scheme based on COVID-19 patients' characteristics: a review of the literature and simulations.
Auteurs : Eleni Karatza ; George Ismailos ; Markos Marangos ; Vangelis KaralisSource :
- Xenobiotica; the fate of foreign compounds in biological systems [ 1366-5928 ] ; 2021.
English descriptors
- KwdEn :
- Antiviral Agents (administration & dosage), Antiviral Agents (pharmacokinetics), Antiviral Agents (therapeutic use), COVID-19 (drug therapy), Computer Simulation (MeSH), Humans (MeSH), Hydroxychloroquine (administration & dosage), Hydroxychloroquine (pharmacokinetics), Hydroxychloroquine (therapeutic use).
- MESH :
- chemical , administration & dosage : Antiviral Agents, Hydroxychloroquine.
- chemical , pharmacokinetics : Antiviral Agents, Hydroxychloroquine.
- chemical , therapeutic use : Antiviral Agents, Hydroxychloroquine.
- drug therapy : COVID-19.
- Computer Simulation, Humans.
Abstract
During the recent COVID-19 outbreak hydroxychloroquine (HCQ) has been proposed as a safe and effective therapeutic option. However, a wide variety of dosing schemes has been applied in the clinical practice and tested in clinical studies. An extended literature survey was performed investigating the pharmacokinetics, the efficacy and safety of HCQ in COVID-19 treatment. Population pharmacokinetic models were retrieved from the literature and after evaluation and assessment one was selected in order to perform simulations. The most commonly applied dosing schemes were explored for patients with different weights and different levels of HCQ clearance impairment. Model-based simulations of HCQ concentrations revealed that high initial doses followed by low and sparse doses may offer significant benefits to patients by decreasing the viral load without reaching levels considered to produce adverse effects. For instance, the dosing scheme proposed for a 70 kg adult with moderate COVID-19 symptoms would be 600 mg upon diagnosis, 400 mg after 12 h, 300 mg after 24 h, 200 mg after 36 h, followed by 200 mg BID for 4 d, followed by 200 mg OD for 5 d. Based on the results from simulations performed and the currently published knowledge regarding HCQ in COVID-19 treatment, this study provides evidence that a high loading dose followed by sparse doses could offer significant benefits to the patients.
DOI: 10.1080/00498254.2020.1824301
PubMed: 32933365
PubMed Central: PMC7544961
Links to Exploration step
pubmed:32933365Le document en format XML
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However, a wide variety of dosing schemes has been applied in the clinical practice and tested in clinical studies. An extended literature survey was performed investigating the pharmacokinetics, the efficacy and safety of HCQ in COVID-19 treatment. Population pharmacokinetic models were retrieved from the literature and after evaluation and assessment one was selected in order to perform simulations. The most commonly applied dosing schemes were explored for patients with different weights and different levels of HCQ clearance impairment. Model-based simulations of HCQ concentrations revealed that high initial doses followed by low and sparse doses may offer significant benefits to patients by decreasing the viral load without reaching levels considered to produce adverse effects. For instance, the dosing scheme proposed for a 70 kg adult with moderate COVID-19 symptoms would be 600 mg upon diagnosis, 400 mg after 12 h, 300 mg after 24 h, 200 mg after 36 h, followed by 200 mg BID for 4 d, followed by 200 mg OD for 5 d. Based on the results from simulations performed and the currently published knowledge regarding HCQ in COVID-19 treatment, this study provides evidence that a high loading dose followed by sparse doses could offer significant benefits to the patients.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">32933365</PMID><DateCompleted><Year>2020</Year><Month>12</Month><Day>31</Day></DateCompleted><DateRevised><Year>2021</Year><Month>05</Month><Day>07</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1366-5928</ISSN><JournalIssue CitedMedium="Internet"><Volume>51</Volume><Issue>2</Issue><PubDate><Year>2021</Year><Month>Feb</Month></PubDate></JournalIssue><Title>Xenobiotica; the fate of foreign compounds in biological systems</Title><ISOAbbreviation>Xenobiotica</ISOAbbreviation></Journal><ArticleTitle>Optimization of hydroxychloroquine dosing scheme based on COVID-19 patients' characteristics: a review of the literature and simulations.</ArticleTitle><Pagination><MedlinePgn>127-138</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1080/00498254.2020.1824301</ELocationID><Abstract><AbstractText>During the recent COVID-19 outbreak hydroxychloroquine (HCQ) has been proposed as a safe and effective therapeutic option. However, a wide variety of dosing schemes has been applied in the clinical practice and tested in clinical studies. An extended literature survey was performed investigating the pharmacokinetics, the efficacy and safety of HCQ in COVID-19 treatment. Population pharmacokinetic models were retrieved from the literature and after evaluation and assessment one was selected in order to perform simulations. The most commonly applied dosing schemes were explored for patients with different weights and different levels of HCQ clearance impairment. Model-based simulations of HCQ concentrations revealed that high initial doses followed by low and sparse doses may offer significant benefits to patients by decreasing the viral load without reaching levels considered to produce adverse effects. For instance, the dosing scheme proposed for a 70 kg adult with moderate COVID-19 symptoms would be 600 mg upon diagnosis, 400 mg after 12 h, 300 mg after 24 h, 200 mg after 36 h, followed by 200 mg BID for 4 d, followed by 200 mg OD for 5 d. Based on the results from simulations performed and the currently published knowledge regarding HCQ in COVID-19 treatment, this study provides evidence that a high loading dose followed by sparse doses could offer significant benefits to the patients.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Karatza</LastName><ForeName>Eleni</ForeName><Initials>E</Initials><Identifier Source="ORCID">https://orcid.org/0000-0001-8406-4121</Identifier><AffiliationInfo><Affiliation>Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Athens, Greece.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ismailos</LastName><ForeName>George</ForeName><Initials>G</Initials><Identifier Source="ORCID">https://orcid.org/0000-0003-1466-4978</Identifier><AffiliationInfo><Affiliation>Experimental-Research Center ELPEN, ELPEN Pharmaceuticals, Pikermi, Greece.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Marangos</LastName><ForeName>Markos</ForeName><Initials>M</Initials><Identifier Source="ORCID">https://orcid.org/0000-0001-5030-2398</Identifier><AffiliationInfo><Affiliation>Division of Infectious Diseases, University Hospital of Patras, Rio, Greece.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Karalis</LastName><ForeName>Vangelis</ForeName><Initials>V</Initials><Identifier Source="ORCID">https://orcid.org/0000-0003-0492-0712</Identifier><AffiliationInfo><Affiliation>Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Athens, Greece.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016454">Review</PublicationType></PublicationTypeList><ArticleDate 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