| Property | Value |
|---|
|
?:abstract
|
-
AIMS: Chloroquine (CQ) has been repurposed to treat coronavirus disease 2019 (COVID-19). Understanding the pharmacokinetics (PK) in COVID-19 patients is essential to study its exposure–efficacy/safety relationship and provide a basis for a possible dosing regimen optimization. SUBJECT AND METHODS: In this study, we used a population-based meta-analysis approach to develop a population PK model to characterize the CQ PK in COVID-19 patients. An open-label, single-center study (ethical review approval number: PJ-NBEY-KY-2020-063-01) was conducted to assess the safety, efficacy, and pharmacokinetics of CQ in patients with COVID-19. The sparse PK data from 50 COVID-19 patients, receiving 500 mg CQ phosphate twice daily for 7 days, were combined with additional CQ PK data from 18 publications. RESULTS: A two-compartment model with first-order oral absorption and first-order elimination and an absorption lag best described the data. Absorption rate (ka) was estimated to be 0.559 h(−1), and a lag time of absorption (ALAG) was estimated to be 0.149 h. Apparent clearance (CL/F) and apparent central volume of distribution (V2/F) was 33.3 l/h and 3630 l. Apparent distribution clearance (Q/F) and volume of distribution of peripheral compartment (Q3/F) were 58.7 l/h and 5120 l. The simulated CQ concentration under five dosing regimens of CQ phosphate were within the safety margin (400 ng/ml). CONCLUSION: Model-based simulation using PK parameters from the COVID-19 patients shows that the concentrations under the currently recommended dosing regimen are below the safety margin for side-effects, which suggests that these dosing regimens are generally safe. The derived population PK model should allow for the assessment of pharmacokinetics–pharmacodynamics (PK-PD) relationships for CQ when given alone or in combination with other agents to treat COVID-19. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00228-020-03032-6.
|
|
is
?:annotates
of
|
|
|
?:creator
|
|
|
?:doi
|
-
10.1007/s00228-020-03032-6
|
|
?:doi
|
|
|
?:journal
|
|
|
?:license
|
|
|
?:pdf_json_files
|
-
document_parses/pdf_json/271f2337f1fc8a9e3811246388ef616ae373d978.json
|
|
?:pmc_json_files
|
-
document_parses/pmc_json/PMC7665884.xml.json
|
|
?:pmcid
|
|
|
?:pmid
|
|
|
?:pmid
|
|
|
?:publication_isRelatedTo_Disease
|
|
|
is
?:relation_isRelatedTo_publication
of
|
|
|
?:sha_id
|
|
|
?:source
|
|
|
?:title
|
-
Population-based meta-analysis of chloroquine: informing chloroquine pharmacokinetics in COVID-19 patients
|
|
?:type
|
|
|
?:year
|
|
![[This page as RDF]](https://research.tib.eu/covid-19/static/rdf-icon.gif){kind=icon}