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Optimization of hydroxychloroquine dosing scheme based on COVID-19 patients’ characteristics: a review of the literature and simulations
Karatza et al., Xenobiotica
Karatza et al., Optimization of hydroxychloroquine dosing scheme based on COVID-19 patients’ characteristics: a review of the.., Xenobiotica
Sep 2020   Source   PDF  
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Analysis of HCQ dosing, suggesting 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 70kg adult with moderate COVID-19 symptoms would be 600mg upon diagnosis, 400mg after 12h, 300mg after 24h, 200mg after 36h, followed by 200mg BID for 4 days, followed by 200mg OD for 5 days.
Suboptimal dosing regimens that do not fully account for the long half-life of HCQ or the patient characteristics are likely contribute to either limited efficacy where therapeutic levels take too long to reach, or significant adverse effects due to excessive dosage.
Karatza et al., 16 Sep 2020, peer-reviewed, 4 authors.
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Abstract: Xenobiotica the fate of foreign compounds in biological systems ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/ixen20 Optimization of hydroxychloroquine dosing scheme based on COVID-19 patients’ characteristics: a review of the literature and simulations Eleni Karatza, George Ismailos, Markos Marangos & Vangelis Karalis To cite this article: Eleni Karatza, George Ismailos, Markos Marangos & Vangelis Karalis (2021) Optimization of hydroxychloroquine dosing scheme based on COVID-19 patients’ characteristics: a review of the literature and simulations, Xenobiotica, 51:2, 127-138, DOI: 10.1080/00498254.2020.1824301 To link to this article: https://doi.org/10.1080/00498254.2020.1824301 View supplementary material Published online: 30 Sep 2020. Submit your article to this journal Article views: 6537 View related articles View Crossmark data Citing articles: 4 View citing articles Full Terms & Conditions of access and use can be found at https://www.tandfonline.com/action/journalInformation?journalCode=ixen20 XENOBIOTICA 2021, VOL. 51, NO. 2, 127–138 https://doi.org/10.1080/00498254.2020.1824301 RESEARCH ARTICLE Optimization of hydroxychloroquine dosing scheme based on COVID-19 patients’ characteristics: a review of the literature and simulations Eleni Karatzaa , George Ismailosb , Markos Marangosc and Vangelis Karalisa a Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Athens, Greece; bExperimentalResearch Center ELPEN, ELPEN Pharmaceuticals, Pikermi, Greece; cDivision of Infectious Diseases, University Hospital of Patras, Rio, Greece ABSTRACT ARTICLE HISTORY 1. Received 31 July 2020 Revised 11 September 2020 Accepted 12 September 2020 2. 3. 4. 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.
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