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All Studies   Meta Analysis    Recent:   

Finding the Dose for Hydroxychloroquine Prophylaxis for COVID-19: The Desperate Search for Effectiveness

Al-Kofahi et al., Clin. Pharmacol. Ther., Jun 1, 2020, doi:10.1002/cpt.1874
Jun 2020  
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HCQ for COVID-19
1st treatment shown to reduce risk in March 2020
 
*, now with p < 0.00000000001 from 411 studies, recognized in 46 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,300+ studies for 75 treatments. c19hcq.org
Analysis of HCQ dosing regimens, recommending:
PrEP: 800mg loading dose followed by 400mg 2 or 3 times weekly to maintain weekly troughs above EC50 in >50% of patients at steady-state.
PEP: 800mg loading dose followed in 6 hours by 600mg, then 600mg daily for 4 more days to achieve daily troughs above EC50 in >50% subjects.
Al-Kofahi et al., 1 Jun 2020, peer-reviewed, 9 authors.
This PaperHCQAll
Finding the Dose for Hydroxychloroquine Prophylaxis for COVID‐19: The Desperate Search for Effectiveness
Mahmoud Al‐kofahi, Pamala Jacobson, David R Boulware, Arthur Matas, Raja Kandaswamy, Mutaz M Jaber, Radha Rajasingham, Jo‐anne H Young, Melanie R Nicol
Clinical Pharmacology & Therapeutics, doi:10.1002/cpt.1874
Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?  Hydroxychloroquine is currently of interest for treatment and prevention of coronavirus disease 2019 (COVID-19). In the absence of therapeutic efficacy targets, optimal dosing is unknown. WHAT QUESTION DID THIS STUDY ADDRESS?  We examined various hydroxychloroquine dosing strategies and compared predicted plasma exposures to in vitro efficacy targets. WHAT DOES THIS STUDY ADD TO OUR KNOW-LEDGE?  Conventional malaria prevention and treatment dosing may not be sufficient to reach plasma concentrations that would be expected to inhibit or suppress severe acute respiratory syndrome coronavirus 2. HOW MIGHT THIS CHANGE CLINICAL PHARMA-COLOGY OR TRANSLATIONAL SCIENCE?  These findings are intended to guide the research community in optimizing dose selection for COVID-19 prevention and early treatment trials.
SUPPORTING INFORMATION Supplementary information accompanies this paper on the Clinical Pharmacology & Therapeutics website (www.cpt-journal.com). FUNDING Support for this study was received from the National Institute of Allergy and Infectious Diseases (K08 AI134262 for M.R.N.); (R01AI140303 for P.A.J.); and (U01AI125003 for D.R.B.). CONFLICT OF INTEREST The authors declared no competing interests for this work. AUTHOR CONTRIBUTIONS
References
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Perinel, Towards optimization of hydroxychloroquine dosing in intensive care unit COVID-19 patients, Clin. Infect. Dis, doi:10.1093/cid/ciaa394
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In an exposure driven, ' 'post‐exposure prophylaxis setting, 800\xa0mg loading dose followed in 6\xa0hours by 600\xa0' 'mg, then 600\xa0mg daily for 4 more days achieved daily troughs above ' 'EC<jats:sub>50</jats:sub> in &gt;\xa050% subjects. These doses are higher than recommended ' 'for malaria chemoprophylaxis, and clinical trials are needed to establish safety and ' 'efficacy.</jats:p>', 'DOI': '10.1002/cpt.1874', 'type': 'journal-article', 'created': {'date-parts': [[2020, 4, 28]], 'date-time': '2020-04-28T21:04:11Z', 'timestamp': 1588107851000}, 'page': '766-769', 'update-policy': 'http://dx.doi.org/10.1002/crossmark_policy', 'source': 'Crossref', 'is-referenced-by-count': 44, 'title': 'Finding the Dose for Hydroxychloroquine Prophylaxis for COVID‐19: The Desperate Search for ' 'Effectiveness', 'prefix': '10.1111', 'volume': '108', 'author': [ { 'given': 'Mahmoud', 'family': 'Al‐Kofahi', 'sequence': 'first', 'affiliation': [ { 'name': 'Department of Experimental and Clinical Pharmacology College of ' 'Pharmacy University of Minnesota Minneapolis Minnesota USA'}]}, { 'given': 'Pamala', 'family': 'Jacobson', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Experimental and Clinical Pharmacology College of ' 'Pharmacy University of Minnesota Minneapolis Minnesota USA'}]}, { 'given': 'David R.', 'family': 'Boulware', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Medicine Medical School University of Minnesota ' 'Minneapolis Minnesota USA'}]}, { 'given': 'Arthur', 'family': 'Matas', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Surgery Medical School University of Minnesota ' 'Minneapolis Minnesota USA'}]}, { 'given': 'Raja', 'family': 'Kandaswamy', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Surgery Medical School University of Minnesota ' 'Minneapolis Minnesota USA'}]}, { 'given': 'Mutaz M.', 'family': 'Jaber', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Experimental and Clinical Pharmacology College of ' 'Pharmacy University of Minnesota Minneapolis Minnesota USA'}]}, { 'given': 'Radha', 'family': 'Rajasingham', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Medicine Medical School University of Minnesota ' 'Minneapolis Minnesota USA'}]}, { 'given': 'Jo‐Anne H.', 'family': 'Young', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Medicine Medical School University of Minnesota ' 'Minneapolis Minnesota USA'}]}, { 'given': 'Melanie R.', 'family': 'Nicol', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Experimental and Clinical Pharmacology College of ' 'Pharmacy University of Minnesota Minneapolis Minnesota USA'}]}], 'member': '311', 'published-online': {'date-parts': [[2020, 6]]}, 'reference': [ {'key': 'e_1_2_9_1_1', 'doi-asserted-by': 'publisher', 'DOI': '10.5582/ddt.2020.01012'}, {'key': 'e_1_2_9_2_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1038/s41421-020-0156-0'}, { 'key': 'e_1_2_9_3_1', 'article-title': 'In vitro antiviral activity and projection of optimized dosing design ' 'of hydroxychloroquine for the treatment of severe acute respiratory ' 'syndrome coronavirus 2 (SARS‐CoV‐2)', 'author': 'Yao X.', 'journal-title': 'Clin. 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