Analgesics
Antiandrogens
Antihistamines
Azvudine
Bromhexine
Budesonide
Colchicine
Conv. Plasma
Curcumin
Famotidine
Favipiravir
Fluvoxamine
Hydroxychlor..
Ivermectin
Lifestyle
Melatonin
Metformin
Minerals
Molnupiravir
Monoclonals
Naso/orophar..
Nigella Sativa
Nitazoxanide
PPIs
Paxlovid
Quercetin
Remdesivir
Thermotherapy
Vitamins
More

Other
Feedback
Home
Top
Abstract
All HCQ studies
Meta analysis
 
Feedback
Home
next
study
previous
study
c19hcq.org COVID-19 treatment researchHCQHCQ (more..)
Melatonin Meta
Metformin Meta
Antihistamines Meta
Azvudine Meta Molnupiravir Meta
Bromhexine Meta
Budesonide Meta
Colchicine Meta Nigella Sativa Meta
Conv. Plasma Meta Nitazoxanide Meta
Curcumin Meta PPIs Meta
Famotidine Meta Paxlovid Meta
Favipiravir Meta Quercetin Meta
Fluvoxamine Meta Remdesivir Meta
Hydroxychlor.. Meta Thermotherapy Meta
Ivermectin Meta

All Studies   Meta Analysis       

Pharmacokinetic Basis of the Hydroxychloroquine Response in COVID-19: Implications for Therapy and Prevention

Tarek et al., European Journal of Drug Metabolism and Pharmacokinetics, doi:10.1007/s13318-020-00640-6
Aug 2020  
  Post
  Facebook
Share
  Source   PDF   All Studies   Meta AnalysisMeta
HCQ for COVID-19
1st treatment shown to reduce risk in March 2020, now with p < 0.00000000001 from 419 studies, recognized in 46 countries.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 109 treatments. c19hcq.org
In Silico analysis of HCQ treatment showing concluding that HCQ may affect viral clearance if administered early enough when the virus is still confined to the pharyngeal cavity; HCQ's effects against SARS-CoV-2 might be exerted more through enhanced cell-mediated immunity than direct antiviral effects; and the effects of HCQ on SARS-CoV-2 viral load may be missed in clinical trials if measurements are not done at the peak of viral replication; and the effects are only evident at dosages able to guarantee a certain plasma drug concentration, i.e., > 400 mg/day.
38 preclinical studies support the efficacy of HCQ for COVID-19:
Tarek et al., 11 Aug 2020, peer-reviewed, 2 authors.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
This PaperHCQAll
Pharmacokinetic Basis of the Hydroxychloroquine Response in COVID-19: Implications for Therapy and Prevention
Mohammad Tarek, Andrea Savarino
European Journal of Drug Metabolism and Pharmacokinetics, doi:10.1007/s13318-020-00640-6
Background and Objectives Chloroquine/hydroxychloroquine has recently been the subject of intense debate regarding its potential antiviral activity against SARS-Cov-2, the etiologic agent of COVID-19. Some report possible curative effects; others do not. Therefore, the objective of this study was to simulate possible scenarios of response to hydroxychloroquine in COVID-19 patients using mathematical modeling. Methods To shed some light on this controversial topic, we simulated hydroxychloroquine-based interventions on virus/host cell dynamics using a basic system of previously published differential equations. Mathematical modeling was implemented using Python programming language v 3.7. Results According to mathematical modeling, hydroxychloroquine may have an impact on the amplitude of the viral load peak and viral clearance if the drug is administered early enough (i.e., when the virus is still confined within the pharyngeal cavity). The effects of chloroquine/hydroxychloroquine may be fully explained only when also considering the capacity of this drug to increase the death rate of SARS-CoV-2-infected cells, in this case by enhancing the cell-mediated immune response. Conclusions These considerations may not only be applied to chloroquine/hydroxychloroquine but may have more general implications for development of anti-COVID-19 combination therapies and prevention strategies through an increased death rate of the infected cells.
References
Accapezzato, Visco, Francavilla, Chloroquine enhances human CD8+ T cell responses against soluble antigens in vivo, J Exp Med
Arnold, Buckner, Hydroxychloroquine for treatment of SARS-CoV-2 infection? Improving our confidence in a model-based approach to dose selection, Clin Transl Sci, doi:10.1111/cts.12797
Baccam, Beauchemin, Macken, Hayden, Perelson, Kinetics of influenza A virus infection in humans, J Virol
Best, Guedj, Madelain, Zika plasma viral dynamics in nonhuman primates provides insights into early infection and antiviral strategies, Proc Natl Acad Sci
Boelaert, Piette, Sperber, The potential place of chloroquine in the treatment of HIV-1-infected patients, J Clin Virol
Borba, Val, Sampaio, Chloroquine diphosphate in two different dosages as adjunctive therapy of hospitalized patients with severe respiratory syndrome in the context of coronavirus (SARS-CoV-2) infection: preliminary safety results of a randomized, double-blinded, phase IIb clinical trial (CloroCovid-19 Study, doi:10.1101/2020.04.07.20056424
Boulware, Post-exposure prophylaxis/preemptive therapy for SARS-coronavirus-2 (COVID-19 PEP)
Carlsson, Hjorton, Abujrais, Rönnblom, Åkerfeldt et al., Measurement of hydroxychloroquine in blood from SLE patients using LC-HRMS-evaluation of whole blood, plasma, and serum as sample matrices, Arthritis Res Ther
Chang, Mo, Yuan, Time kinetics of viral clearance and resolution of symptoms in novel coronavirus infection, Am J Respir Crit Care Med
Chen, Liu, Liu, A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19 (COVID-19), J Zhejiang Univ (Med Sci, doi:10.3785/j.issn.1008-9292.2020.03.03
Fan, Zhang, Liu, Connecting hydroxychloroquine in vitro antiviral activity to in vivo concentration for prediction of antiviral effect: a critical step in treating COVID-19 patients, Clin Infect Dis, doi:10.1093/cid/ciaa623
Fong, Wright, Hemozoin and antimalarial drug discovery, Future Med Chem
Gao, Tian, Yang, Breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies, Biosci Trends, doi:10.5582/bst.2020.01047
Garcia-Cremades, Solans, Hughes, Ernest, Wallender et al., Optimizing hydroxychloroquine dosing for patients with COVID-19: an integrative modeling approach for effective drug repurposing, Clin Pharmacol Ther, doi:10.1002/cpt.1856
Gautret, Lagier, Parola, Meddeb, Mailhe et al., Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial, Int J Antimicrob Agents
Gil-Moles, Basu, Büssing, Hoffmeister, Türck et al., Gold metallodrugs to fight the corona virus: inhibitory effects on the SpikeACE2 interaction and on PLpro protease activity by auranofin and gold organometallics, doi:10.26434/chemrxiv.12488390.v1
Gonçalves, Bertrand, Ke, Comets, De Lamballerie et al., Timing of antiviral treatment initiation is critical to reduce SARS-CoV-2 viral load, CPT Pharmacometr Syst Pharmacol, doi:10.1002/psp4.12543
Guérin, Lévy, Thomas, Lardenois, Lacrosse et al., Azithromycin and hydroxychloroquine accelerate recovery of outpatients with mild/moderate COVID-19, doi:10.20944/preprints202005.0486.v1
Huang, Tang, Pang, Li, Ma et al., Treating COVID-19 with chloroquine, J Mol Cell Biol, doi:10.1093/jmcb/mjaa014
Hunter, Matplotlib: a 2D graphics environment, Comput Sci Eng
Kim, Ejima, Ito, Modelling SARS-CoV-2 dynamics: implications for therapy, medRxiv, doi:10.1101/2020.03.23.20040493
Langtangen, Pedersen, Scaling of differential equations, doi:10.1007/978-3-319-32726-6
Lee, Son, Peck, Can post-exposure prophylaxis for COVID-19 be considered as one of outbreak response strategies in long-term care hospitals?, Int J Antimicrob Agents, doi:10.1016/j.ijantimicag.2020.105988
Li, Xu, Liu, The within-host viral kinetics of SARS-CoV-2, Math Biosci Eng, doi:10.1101/2020.02.29.965418
Lim, Im, Cho, Pharmacokinetics of hydroxychloroquine and its clinical implications in chemoprophylaxis against malaria caused by Plasmodium vivax, Antimicrob Agents Chemother, doi:10.1128/AAC.00339-08
Morita, Takahashi, Yoshida, Yokota, Population pharmacokinetics of hydroxychloroquine in Japanese patients with cutaneous or systemic lupus erythematosus, Ther Drug Monit
Oscanoa, Romero-Ortuno, Carvajal, Savarino, A pharmacological perspective of chloroquine in SARS-CoV-2 infection, Int J Antimicrob Agents, doi:10.1016/j.ijantimicag.2020.106078
Pagliano, Piazza, Caro, Ascione, Filippelli, Is hydroxychloroquine a possible postexposure prophylaxis drug to limit the transmission to healthcare workers exposed to coronavirus disease 2019?, Clin Infect Dis, doi:10.1093/cid/ciaa320
Perelson, Rong, Hayden, Combination antiviral therapy for influenza: predictions from modeling of human infections, J Infect Dis
Principi, Esposito, Chloroquine or hydroxychloroquine for prophylaxis of COVID-19, Lancet Infect Dis, doi:10.1016/S1473-3099(20)30296-6
Pussard, Lepers, Clavier, Efficacy of a loading dose of oral chloroquine in a 36-hour treatment schedule for uncomplicated plasmodium falciparum malaria, Antimicrob Agents Chemother, doi:10.1128/aac.35.3.406
Pötsch, Fischer, Müller, Lexikon bedeutender Chemiker
Rong, Perelson, Modeling latently infected cell activation: viral and latent reservoir persistence, and viral blips in HIV-infected patients on potent therapy, PLoS Comput Biol, doi:10.1371/journal.pcbi.1000533
Rothan, Stone, Natekar, Kumari, Arora et al., The FDA-approved gold drug Auranofin inhibits novel coronavirus (SARS-COV-2) replication and attenuates inflammation in human cells, Virology, doi:10.1016/j.virol.2020.05.002
Sarayani, Cicali, Henriksen, Brown, Safety signals for QT prolongation or Torsades de Pointes associated with azithromycin with or without chloroquine or hydroxychloroquine, Res Soc Adm Pharm, doi:10.1016/j.sapharm.2020.04.016
Savarino, Boelaert, Cassone, Majori, Cauda, Effects of chloroquine on viral infections: an old drug against today's diseases?, Lancet Infect Dis
Savarino, Bottarel, Malavasi, Dianzani, Role of CD38 in HIV-1 infection: an epiphenomenon of T-cell activation or an active player in virus/host interactions?, Aids
Savarino, Buonavoglia, Norelli, Trani, Cassone, Potential therapies for coronaviruses, Expert Opin Ther Pat, doi:10.1517/13543776.16.9.1269
Shytaj, Chirullo, Wagner, Ferrari, Sgarbanti et al., Investigational treatment suspension and enhanced cell-mediated immunity at rebound followed by drug-free remission of simian AIDS, Retrovirology
Shytaj, Norelli, Chirullo, A highly intensified ART regimen induces long-term viral suppression and restriction of the viral reservoir in a simian AIDS model, PLoS Pathog, doi:10.1371/journal.ppat.1002774
Smit, Peeters, Van Den Anker, Knibbe, Chloroquine for SARS-CoV-2: implications of its unique pharmacokinetic and safety properties, Clin Pharmacokinet
Smit, Peeters, Van Den Anker, Knibbe, Chloroquine for SARS-CoV-2: implications of its unique pharmacokinetic and safety properties, Clin Pharmacokinet, doi:10.1007/s40262-020-00891-1
Virtanen, Gommers, Oliphant, Haberland, Reddy et al., SciPy 1.0: fundamental algorithms for scientific computing in Python, Nat Methods
Wallace, Hahn, Dubois' lupus erythematosus
Walt, Colbert, Varoquaux, The NumPy array: a structure for efficient numerical computation, Comput Sci Eng
Wang, Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro, Cell Res, doi:10.1038/s41422-020-0282-0
Yao, Ye, Zhang, Cui, Huang et al., 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), Clin Infect Dis, doi:10.1093/cid/ciaa237
Yen, Liao, Hsiao, Kao, Chen et al., Modeling the early events of severe acute respiratory syndrome coronavirus infection in vitro, J Virol
Zou, Ruan, Huang, Liang, Huang et al., SARS-CoV-2 viral load in upper respiratory specimens of infected patients, N Engl J Med
{ 'indexed': {'date-parts': [[2024, 4, 25]], 'date-time': '2024-04-25T15:08:50Z', 'timestamp': 1714057730102}, 'reference-count': 49, 'publisher': 'Springer Science and Business Media LLC', 'issue': '6', 'license': [ { 'start': { 'date-parts': [[2020, 8, 11]], 'date-time': '2020-08-11T00:00:00Z', 'timestamp': 1597104000000}, 'content-version': 'tdm', 'delay-in-days': 0, 'URL': 'https://www.springer.com/tdm'}, { 'start': { 'date-parts': [[2020, 8, 11]], 'date-time': '2020-08-11T00:00:00Z', 'timestamp': 1597104000000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://www.springer.com/tdm'}], 'content-domain': {'domain': ['link.springer.com'], 'crossmark-restriction': False}, 'published-print': {'date-parts': [[2020, 12]]}, 'DOI': '10.1007/s13318-020-00640-6', 'type': 'journal-article', 'created': {'date-parts': [[2020, 8, 11]], 'date-time': '2020-08-11T14:07:32Z', 'timestamp': 1597154852000}, 'page': '715-723', 'update-policy': 'http://dx.doi.org/10.1007/springer_crossmark_policy', 'source': 'Crossref', 'is-referenced-by-count': 13, 'title': 'Pharmacokinetic Basis of the Hydroxychloroquine Response in COVID-19: Implications for Therapy ' 'and Prevention', 'prefix': '10.1007', 'volume': '45', 'author': [ {'given': 'Mohammad', 'family': 'Tarek', 'sequence': 'first', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0003-0983-3693', 'authenticated-orcid': False, 'given': 'Andrea', 'family': 'Savarino', 'sequence': 'additional', 'affiliation': []}], 'member': '297', 'published-online': {'date-parts': [[2020, 8, 11]]}, 'reference': [ { 'key': '640_CR1', 'volume-title': 'Lexikon bedeutender Chemiker', 'author': 'WR Pötsch', 'year': '1988', 'unstructured': 'Pötsch WR, Fischer A, Müller W. Lexikon bedeutender Chemiker. New Delhi: ' 'Anamika Publishers & Distributors; 1988.'}, { 'key': '640_CR2', 'volume-title': 'Dubois’ lupus erythematosus', 'year': '2007', 'unstructured': 'Wallace DJ, Hahn B, editors. Dubois’ lupus erythematosus. Philadelphia: ' 'Lippincott Williams & Wilkins; 2007.'}, { 'issue': '11', 'key': '640_CR3', 'doi-asserted-by': 'publisher', 'first-page': '722', 'DOI': '10.1016/S1473-3099(03)00806-5', 'volume': '3', 'author': 'A Savarino', 'year': '2003', 'unstructured': 'Savarino A, Boelaert JR, Cassone A, Majori G, Cauda R. Effects of ' 'chloroquine on viral infections: an old drug against today’s diseases? ' 'Lancet Infect Dis. 2003;3(11):722–7.', 'journal-title': 'Lancet Infect Dis'}, { 'issue': '12', 'key': '640_CR4', 'doi-asserted-by': 'publisher', 'first-page': '1437', 'DOI': '10.4155/fmc.13.113', 'volume': '5', 'author': 'KY Fong', 'year': '2013', 'unstructured': 'Fong KY, Wright DW. Hemozoin and antimalarial drug discovery. Future Med ' 'Chem. 2013;5(12):1437–50.', 'journal-title': 'Future Med Chem'}, { 'issue': '4', 'key': '640_CR5', 'doi-asserted-by': 'publisher', 'first-page': '642', 'DOI': '10.1111/cts.12797', 'volume': '13', 'author': 'SLM Arnold', 'year': '2020', 'unstructured': 'Arnold SLM, Buckner F. Hydroxychloroquine for treatment of SARS-CoV-2 ' 'infection? Improving our confidence in a model-based approach to dose ' 'selection.\xa0Clin Transl Sci. 2020;13(4):642–5. ' 'https://doi.org/10.1111/cts.12797.', 'journal-title': 'Clin Transl Sci'}, { 'key': '640_CR6', 'doi-asserted-by': 'publisher', 'first-page': '105949', 'DOI': '10.1016/j.ijantimicag.2020.105949', 'volume': '20', 'author': 'P Gautret', 'year': '2020', 'unstructured': 'Gautret P, Lagier JC, Parola P, Meddeb L, Mailhe M, Doudier B, Courjon ' 'J, Giordanengo V, Vieira VE, Dupont HT, Honoré S. Hydroxychloroquine and ' 'azithromycin as a treatment of COVID-19: results of an open-label ' 'non-randomized clinical trial. Int J Antimicrob Agents. 2020;20:105949.', 'journal-title': 'Int J Antimicrob Agents'}, { 'issue': '2', 'key': '640_CR7', 'doi-asserted-by': 'publisher', 'first-page': '259', 'DOI': '10.1097/FTD.0000000000000261', 'volume': '38', 'author': 'S Morita', 'year': '2016', 'unstructured': 'Morita S, Takahashi T, Yoshida Y, Yokota N. Population pharmacokinetics ' 'of hydroxychloroquine in Japanese patients with cutaneous or systemic ' 'lupus erythematosus. Ther Drug Monit. 2016;38(2):259–67.', 'journal-title': 'Ther Drug Monit'}, { 'issue': '6', 'key': '640_CR8', 'doi-asserted-by': 'publisher', 'first-page': '659', 'DOI': '10.1007/s40262-020-00891-1', 'volume': '59', 'author': 'C Smit', 'year': '2020', 'unstructured': 'Smit C, Peeters MYM, van den Anker JN, Knibbe CAJ. Chloroquine for ' 'SARS-CoV-2: implications of its unique pharmacokinetic and safety ' 'properties. Clin Pharmacokinet. 2020;59(6):659–69.', 'journal-title': 'Clin Pharmacokinet'}, { 'key': '640_CR9', 'doi-asserted-by': 'publisher', 'first-page': '106078', 'DOI': '10.1016/j.ijantimicag.2020.106078', 'volume': '4', 'author': 'TJ Oscanoa', 'year': '2020', 'unstructured': 'Oscanoa TJ, Romero-Ortuno R, Carvajal A, Savarino A. A pharmacological ' 'perspective of chloroquine in SARS-CoV-2 infection. Int J Antimicrob ' 'Agents. 2020;4:106078. ' 'https://doi.org/10.1016/j.ijantimicag.2020.106078.', 'journal-title': 'Int J Antimicrob Agents'}, { 'issue': '3', 'key': '640_CR10', 'doi-asserted-by': 'publisher', 'first-page': '406', 'DOI': '10.1128/aac.35.3.406', 'volume': '35', 'author': 'E Pussard', 'year': '1991', 'unstructured': 'Pussard E, Lepers JP, Clavier F, et al. Efficacy of a loading dose of ' 'oral chloroquine in a 36-hour treatment schedule for uncomplicated ' 'plasmodium falciparum malaria.\xa0Antimicrob Agents Chemother. ' '1991;35(3):406–9. https://doi.org/10.1128/aac.35.3.406.', 'journal-title': 'Antimicrob Agents Chemother'}, { 'issue': '4', 'key': '640_CR11', 'doi-asserted-by': 'publisher', 'first-page': '1468', 'DOI': '10.1128/AAC.00339-08', 'volume': '53', 'author': 'HS Lim', 'year': '2009', 'unstructured': 'Lim HS, Im JS, Cho JY, et al. Pharmacokinetics of hydroxychloroquine and ' 'its clinical implications in chemoprophylaxis against malaria caused by ' 'Plasmodium vivax. Antimicrob Agents Chemother. 2009;53(4):1468–75. ' 'https://doi.org/10.1128/AAC.00339-08.', 'journal-title': 'Antimicrob Agents Chemother.'}, { 'issue': '3', 'key': '640_CR12', 'doi-asserted-by': 'publisher', 'first-page': '137', 'DOI': '10.1016/S1386-6532(00)00140-2', 'volume': '20', 'author': 'JR Boelaert', 'year': '2001', 'unstructured': 'Boelaert JR, Piette J, Sperber K. The potential place of chloroquine in ' 'the treatment of HIV-1-infected patients. J Clin Virol. ' '2001;20(3):137–40.', 'journal-title': 'J Clin Virol'}, { 'issue': '9', 'key': '640_CR13', 'doi-asserted-by': 'publisher', 'first-page': '1079', 'DOI': '10.1097/00002030-200006160-00004', 'volume': '14', 'author': 'A Savarino', 'year': '2000', 'unstructured': 'Savarino A, Bottarel F, Malavasi F, Dianzani U. Role of CD38 in HIV-1 ' 'infection: an epiphenomenon of T-cell activation or an active player in ' 'virus/host interactions? Aids. 2000;14(9):1079–89.', 'journal-title': 'Aids'}, { 'issue': '6', 'key': '640_CR14', 'doi-asserted-by': 'publisher', 'first-page': '817', 'DOI': '10.1084/jem.20051106', 'volume': '202', 'author': 'D Accapezzato', 'year': '2005', 'unstructured': 'Accapezzato D, Visco V, Francavilla V, et al. Chloroquine enhances human ' 'CD8+ T cell responses against soluble antigens in vivo. J Exp Med. ' '2005;202(6):817–28.', 'journal-title': 'J Exp Med'}, { 'issue': '9', 'key': '640_CR15', 'doi-asserted-by': 'publisher', 'first-page': '1150', 'DOI': '10.1164/rccm.202003-0524LE', 'volume': '201', 'author': 'D Chang', 'year': '2020', 'unstructured': 'Chang D, Mo G, Yuan X, et al. Time kinetics of viral clearance and ' 'resolution of symptoms in novel coronavirus infection. Am J Respir Crit ' 'Care Med. 2020;201(9):1150–2', 'journal-title': 'Am J Respir Crit Care Med'}, { 'key': '640_CR16', 'doi-asserted-by': 'publisher', 'DOI': '10.1038/s41422-020-0282-0', 'author': 'M Wang', 'year': '2020', 'unstructured': 'Wang M, et al. Remdesivir and chloroquine effectively inhibit the ' 'recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020. ' 'https://doi.org/10.1038/s41422-020-0282-0.', 'journal-title': 'Cell Res'}, { 'key': '640_CR17', 'doi-asserted-by': 'publisher', 'DOI': '10.1093/cid/ciaa237', 'author': 'X Yao', 'year': '2020', 'unstructured': 'Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, Liu X, Zhao L, Dong E, Song ' 'C, Zhan S. 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). Clin Infect Dis. 2020. ' 'https://doi.org/10.1093/cid/ciaa237.', 'journal-title': 'Clin Infect Dis'}, { 'key': '640_CR18', 'doi-asserted-by': 'publisher', 'DOI': '10.1002/psp4.12543', 'author': 'A Gonçalves', 'year': '2020', 'unstructured': 'Gonçalves A, Bertrand J, Ke R, Comets E, de Lamballerie X, Malvy D, ' 'Pizzorno A, Terrier O, Rosa Calatrava M, Mentré F, Smith P. Timing of ' 'antiviral treatment initiation is critical to reduce SARS-CoV-2 viral ' 'load. CPT Pharmacometr Syst Pharmacol. 2020. ' 'https://doi.org/10.1002/psp4.12543.', 'journal-title': 'CPT Pharmacometr Syst Pharmacol'}, { 'issue': '33', 'key': '640_CR19', 'doi-asserted-by': 'publisher', 'first-page': '8847', 'DOI': '10.1073/pnas.1704011114', 'volume': '114', 'author': 'K Best', 'year': '2017', 'unstructured': 'Best K, Guedj J, Madelain V, et al. Zika plasma viral dynamics in ' 'nonhuman primates provides insights into early infection and antiviral ' 'strategies. Proc Natl Acad Sci. 2017;114(33):8847–52.', 'journal-title': 'Proc Natl Acad Sci'}, { 'key': '640_CR20', 'doi-asserted-by': 'publisher', 'first-page': '2853', 'DOI': '10.1101/2020.02.29.965418', 'volume': '17', 'author': 'C Li', 'year': '2020', 'unstructured': 'Li C, Xu J, Liu J, et al. The within-host viral kinetics of SARS-CoV-2. ' 'Math Biosci Eng. 2020;17:2853–61. ' 'https://doi.org/10.1101/2020.02.29.965418.', 'journal-title': 'Math Biosci Eng.'}, { 'key': '640_CR21', 'doi-asserted-by': 'publisher', 'DOI': '10.1101/2020.03.23.20040493', 'author': 'KS Kim', 'year': '2020', 'unstructured': 'Kim KS, Ejima K, Ito Y, et al. Modelling SARS-CoV-2 dynamics: ' 'implications for therapy. medRxiv. 2020;. ' 'https://doi.org/10.1101/2020.03.23.20040493.', 'journal-title': 'medRxiv.'}, { 'issue': '10', 'key': '640_CR22', 'doi-asserted-by': 'publisher', 'first-page': 'e1000533', 'DOI': '10.1371/journal.pcbi.1000533', 'volume': '5', 'author': 'L Rong', 'year': '2009', 'unstructured': 'Rong L, Perelson AS. Modeling latently infected cell activation: viral ' 'and latent reservoir persistence, and viral blips in HIV-infected ' 'patients on potent therapy. PLoS Comput Biol. 2009;5(10):e1000533. ' 'https://doi.org/10.1371/journal.pcbi.1000533.', 'journal-title': 'PLoS Comput Biol.'}, { 'issue': '6', 'key': '640_CR23', 'doi-asserted-by': 'publisher', 'first-page': 'e1002774', 'DOI': '10.1371/journal.ppat.1002774', 'volume': '8', 'author': 'IL Shytaj', 'year': '2012', 'unstructured': 'Shytaj IL, Norelli S, Chirullo B, et al. A highly intensified ART ' 'regimen induces long-term viral suppression and restriction of the viral ' 'reservoir in a simian AIDS model.\xa0PLoS Pathog. 2012;8(6):e1002774. ' 'https://doi.org/10.1371/journal.ppat.1002774.', 'journal-title': 'PLoS Pathog.'}, { 'issue': '15', 'key': '640_CR24', 'doi-asserted-by': 'publisher', 'first-page': '7590', 'DOI': '10.1128/JVI.01623-05', 'volume': '80', 'author': 'P Baccam', 'year': '2006', 'unstructured': 'Baccam P, Beauchemin C, Macken CA, Hayden FG, Perelson AS. Kinetics of ' 'influenza A virus infection in humans. J Virol. 2006;80(15):7590–9.', 'journal-title': 'J Virol'}, { 'issue': '11', 'key': '640_CR25', 'doi-asserted-by': 'publisher', 'first-page': '1642', 'DOI': '10.1093/infdis/jis265', 'volume': '205', 'author': 'AS Perelson', 'year': '2012', 'unstructured': 'Perelson AS, Rong L, Hayden FG. Combination antiviral therapy for ' 'influenza: predictions from modeling of human infections. J Infect Dis. ' '2012;205(11):1642–5.', 'journal-title': 'J Infect Dis'}, { 'key': '640_CR26', 'doi-asserted-by': 'publisher', 'first-page': '1', 'DOI': '10.1186/s13075-020-02211-1', 'volume': '22', 'author': 'H Carlsson', 'year': '2020', 'unstructured': 'Carlsson H, Hjorton K, Abujrais S, Rönnblom L, Åkerfeldt T, Kultima K. ' 'Measurement of hydroxychloroquine in blood from SLE patients using ' 'LC-HRMS—evaluation of whole blood, plasma, and serum as sample matrices. ' 'Arthritis Res Ther. 2020;22:1–9.', 'journal-title': 'Arthritis Res Ther'}, { 'issue': '9', 'key': '640_CR27', 'doi-asserted-by': 'publisher', 'first-page': '1269', 'DOI': '10.1517/13543776.16.9.1269', 'volume': '16', 'author': 'A Savarino', 'year': '2006', 'unstructured': 'Savarino A, Buonavoglia C, Norelli S, Trani LD, Cassone A. Potential ' 'therapies for coronaviruses.\xa0Expert Opin Ther Pat. ' '2006;16(9):1269–88. https://doi.org/10.1517/13543776.16.9.1269.', 'journal-title': 'Expert Opin Ther Pat'}, { 'issue': '3', 'key': '640_CR28', 'doi-asserted-by': 'publisher', 'first-page': '261', 'DOI': '10.1038/s41592-019-0686-2', 'volume': '17', 'author': 'P Virtanen', 'year': '2020', 'unstructured': 'Virtanen P, Gommers R, Oliphant TE, Haberland M, Reddy T, Cournapeau D, ' 'Burovski E, Peterson P, Weckesser W, Bright J. van der Walt SJ. SciPy ' '1.0: fundamental algorithms for scientific computing in Python. Nat ' 'Methods. 2020;17(3):261–72.', 'journal-title': 'Nat Methods.'}, { 'issue': '2', 'key': '640_CR29', 'doi-asserted-by': 'publisher', 'first-page': '22', 'DOI': '10.1109/MCSE.2011.37', 'volume': '13', 'author': 'SV Walt', 'year': '2011', 'unstructured': 'Walt SV, Colbert SC, Varoquaux G. The NumPy array: a structure for ' 'efficient numerical computation. Comput Sci Eng. 2011;13(2):22–30.', 'journal-title': 'Comput Sci Eng'}, { 'issue': '3', 'key': '640_CR30', 'doi-asserted-by': 'publisher', 'first-page': '90', 'DOI': '10.1109/MCSE.2007.55', 'volume': '9', 'author': 'JD Hunter', 'year': '2007', 'unstructured': 'Hunter JD. Matplotlib: a 2D graphics environment. Comput Sci Eng. ' '2007;9(3):90–5.', 'journal-title': 'Comput Sci Eng'}, { 'key': '640_CR31', 'doi-asserted-by': 'publisher', 'DOI': '10.1007/978-3-319-32726-6', 'volume-title': 'Scaling of differential equations', 'author': 'HP Langtangen', 'year': '2016', 'unstructured': 'Langtangen HP, Pedersen GK. Scaling of differential equations. Berlin: ' 'Springer Nature; 2016. https://doi.org/10.1007/978-3-319-32726-6.'}, { 'key': '640_CR32', 'doi-asserted-by': 'publisher', 'DOI': '10.1093/cid/ciaa623', 'author': 'J Fan', 'year': '2020', 'unstructured': 'Fan J, Zhang X, Liu J, et al. Connecting hydroxychloroquine in vitro ' 'antiviral activity to in vivo concentration for prediction of antiviral ' 'effect: a critical step in treating COVID-19 patients. Clin Infect Dis. ' '2020. https://doi.org/10.1093/cid/ciaa623.', 'journal-title': 'Clin Infect Dis.'}, { 'key': '640_CR33', 'doi-asserted-by': 'publisher', 'unstructured': 'Guérin V, Lévy P, Thomas JL, Lardenois T, Lacrosse P, Sarrazin E, de ' 'Andreis NR, Wonner M. Azithromycin and hydroxychloroquine accelerate ' 'recovery of outpatients with mild/moderate COVID-19. Preprints. 2020. ' 'https://doi.org/10.20944/preprints202005.0486.v1.', 'DOI': '10.20944/preprints202005.0486.v1'}, { 'key': '640_CR34', 'doi-asserted-by': 'publisher', 'DOI': '10.1002/cpt.1856', 'author': 'M Garcia-Cremades', 'year': '2020', 'unstructured': 'Garcia-Cremades M, Solans BP, Hughes E, Ernest JP, Wallender E, Aweeka ' 'F, Luetkemeyer AF, Savic RM. Optimizing hydroxychloroquine dosing for ' 'patients with COVID-19: an integrative modeling approach for effective ' 'drug repurposing. Clin Pharmacol Ther. 2020. ' 'https://doi.org/10.1002/cpt.1856.', 'journal-title': 'Clin Pharmacol Ther'}, { 'key': '640_CR35', 'doi-asserted-by': 'publisher', 'first-page': '1', 'DOI': '10.1007/s40262-020-00891-1', 'volume': '18', 'author': 'C Smit', 'year': '2020', 'unstructured': 'Smit C, Peeters MY, van den Anker JN, Knibbe CA. Chloroquine for ' 'SARS-CoV-2: implications of its unique pharmacokinetic and safety ' 'properties. Clin Pharmacokinet. 2020;18:1. ' 'https://doi.org/10.1007/s40262-020-00891-1.', 'journal-title': 'Clin Pharmacokinet'}, { 'key': '640_CR36', 'doi-asserted-by': 'publisher', 'unstructured': 'Chen J, Liu D, Liu L, et al. A pilot study of hydroxychloroquine in ' 'treatment of patients with common coronavirus disease-19 (COVID-19). J ' 'Zhejiang Univ (Med Sci). Published online March 6, 2020. ' 'https://doi.org/10.3785/j.issn.1008-9292.2020.03.03.', 'DOI': '10.3785/j.issn.1008-9292.2020.03.03'}, { 'issue': '4', 'key': '640_CR37', 'doi-asserted-by': 'publisher', 'first-page': '322', 'DOI': '10.1093/jmcb/mjaa014', 'volume': '12', 'author': 'M Huang', 'year': '2020', 'unstructured': 'Huang M, Tang T, Pang P, Li M, Ma R, Lu J, Shu J, You Y, Chen B, Liang ' 'J, Hong Z. Treating COVID-19 with chloroquine. J Mol Cell Biol. ' '2020;12(4):322–5. https://doi.org/10.1093/jmcb/mjaa014.', 'journal-title': 'J Mol Cell Biol'}, { 'key': '640_CR38', 'doi-asserted-by': 'publisher', 'DOI': '10.5582/bst.2020.01047', 'author': 'J Gao', 'year': '2020', 'unstructured': 'Gao J, Tian Z, Yang X. Breakthrough: chloroquine phosphate has shown ' 'apparent efficacy in treatment of COVID-19 associated pneumonia in ' 'clinical studies. Biosci Trends. 2020. ' 'https://doi.org/10.5582/bst.2020.01047.', 'journal-title': 'Biosci Trends'}, { 'key': '640_CR39', 'doi-asserted-by': 'publisher', 'unstructured': 'Borba MGS, Almeida Val F, Sampaio VS, et al. Chloroquine diphosphate in ' 'two different dosages as adjunctive therapy of hospitalized patients ' 'with severe respiratory syndrome in the context of coronavirus ' '(SARS-CoV-2) infection: preliminary safety results of a randomized, ' 'double-blinded, phase IIb clinical trial (CloroCovid-19 Study). medRxiv. ' 'April 2020. https://doi.org/10.1101/2020.04.07.20056424.', 'DOI': '10.1101/2020.04.07.20056424'}, { 'issue': '12', 'key': '640_CR40', 'doi-asserted-by': 'publisher', 'first-page': '1177', 'DOI': '10.1056/NEJMc2001737', 'volume': '382', 'author': 'L Zou', 'year': '2020', 'unstructured': 'Zou L, Ruan F, Huang M, Liang L, Huang H, Hong Z, Yu J, Kang M, Song Y, ' 'Xia J, Guo Q. SARS-CoV-2 viral load in upper respiratory specimens of ' 'infected patients. N Engl J Med. 2020;382(12):1177–9.', 'journal-title': 'N Engl J Med'}, { 'key': '640_CR41', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.sapharm.2020.04.016', 'author': 'A Sarayani', 'year': '2020', 'unstructured': 'Sarayani A, Cicali B, Henriksen CH, Brown JD. Safety signals for QT ' 'prolongation or Torsades de Pointes associated with azithromycin with or ' 'without chloroquine or hydroxychloroquine. Res Soc Adm Pharm. 2020. ' 'https://doi.org/10.1016/j.sapharm.2020.04.016.', 'journal-title': 'Res Soc Adm Pharm'}, { 'key': '640_CR42', 'unstructured': 'Boulware D. Post-exposure prophylaxis/preemptive therapy for ' 'SARS-coronavirus-2 (COVID-19 PEP). Minneapolis: University of Minnesota. ' 'https://clinicaltrials.gov/ct2/show/NCT04308668. Accessed 27 Apr 2020.'}, { 'key': '640_CR43', 'doi-asserted-by': 'publisher', 'first-page': '105988', 'DOI': '10.1016/j.ijantimicag.2020.105988', 'volume': '17', 'author': 'SH Lee', 'year': '2020', 'unstructured': 'Lee SH, Son H, Peck KR. Can post-exposure prophylaxis for COVID-19 be ' 'considered as one of outbreak response strategies in long-term care ' 'hospitals? Int J Antimicrob Agents. 2020;17:105988. ' 'https://doi.org/10.1016/j.ijantimicag.2020.105988.', 'journal-title': 'Int J Antimicrob Agents'}, { 'key': '640_CR44', 'doi-asserted-by': 'publisher', 'DOI': '10.1093/cid/ciaa320', 'author': 'P Pagliano', 'year': '2020', 'unstructured': 'Pagliano P, Piazza O, De Caro F, Ascione T, Filippelli A. Is ' 'hydroxychloroquine a possible postexposure prophylaxis drug to limit the ' 'transmission to healthcare workers exposed to coronavirus disease 2019? ' 'Clin Infect Dis. 2020. https://doi.org/10.1093/cid/ciaa320.', 'journal-title': 'Clin Infect Dis'}, { 'key': '640_CR45', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/S1473-3099(20)30296-6', 'author': 'N Principi', 'year': '2020', 'unstructured': 'Principi N, Esposito S. Chloroquine or hydroxychloroquine for ' 'prophylaxis of COVID-19. Lancet Infect Dis. 2020. ' 'https://doi.org/10.1016/S1473-3099(20)30296-6.', 'journal-title': 'Lancet Infect Dis'}, { 'issue': '6', 'key': '640_CR46', 'doi-asserted-by': 'publisher', 'first-page': '2684', 'DOI': '10.1128/JVI.80.6.2684-2693.2006', 'volume': '80', 'author': 'YT Yen', 'year': '2006', 'unstructured': 'Yen YT, Liao F, Hsiao CH, Kao CL, Chen YC, Wu-Hsieh BA. Modeling the ' 'early events of severe acute respiratory syndrome coronavirus infection ' 'in vitro. J Virol. 2006;80(6):2684–93.', 'journal-title': 'J Virol'}, { 'key': '640_CR47', 'doi-asserted-by': 'publisher', 'unstructured': 'Gil-Moles M, Basu U, Büssing R, Hoffmeister H, Türck S, Varchmin A, et ' 'al. Gold metallodrugs to fight the corona virus: inhibitory effects on ' 'the SpikeACE2 interaction and on PLpro protease activity by auranofin ' 'and gold organometallics. ChemRxiv. 2020. Preprint. ' 'https://doi.org/10.26434/chemrxiv.12488390.v1.', 'DOI': '10.26434/chemrxiv.12488390.v1'}, { 'issue': '1', 'key': '640_CR48', 'doi-asserted-by': 'publisher', 'first-page': '71', 'DOI': '10.1186/1742-4690-10-71', 'volume': '10', 'author': 'IL Shytaj', 'year': '2013', 'unstructured': 'Shytaj IL, Chirullo B, Wagner W, Ferrari MG, Sgarbanti R, Della Corte A, ' 'LaBranche C, Lopalco L, Palamara AT, Montefiori D, Lewis MG. ' 'Investigational treatment suspension and enhanced cell-mediated immunity ' 'at rebound followed by drug-free remission of simian AIDS. ' 'Retrovirology. 2013;10(1):71.', 'journal-title': 'Retrovirology'}, { 'key': '640_CR49', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.virol.2020.05.002', 'author': 'HA Rothan', 'year': '2020', 'unstructured': 'Rothan HA, Stone S, Natekar J, Kumari P, Arora K, Kumar M. The ' 'FDA-approved gold drug Auranofin inhibits novel coronavirus (SARS-COV-2) ' 'replication and attenuates inflammation in human cells. Virology. 2020. ' 'https://doi.org/10.1016/j.virol.2020.05.002.', 'journal-title': 'Virology'}], 'container-title': 'European Journal of Drug Metabolism and Pharmacokinetics', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://link.springer.com/content/pdf/10.1007/s13318-020-00640-6.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/article/10.1007/s13318-020-00640-6/fulltext.html', 'content-type': 'text/html', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/content/pdf/10.1007/s13318-020-00640-6.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2021, 8, 10]], 'date-time': '2021-08-10T23:19:13Z', 'timestamp': 1628637553000}, 'score': 1, 'resource': {'primary': {'URL': 'https://link.springer.com/10.1007/s13318-020-00640-6'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2020, 8, 11]]}, 'references-count': 49, 'journal-issue': {'issue': '6', 'published-print': {'date-parts': [[2020, 12]]}}, 'alternative-id': ['640'], 'URL': 'http://dx.doi.org/10.1007/s13318-020-00640-6', 'relation': { 'has-preprint': [ { 'id-type': 'doi', 'id': '10.1101/2020.04.23.20076471', 'asserted-by': 'object'}]}, 'ISSN': ['0378-7966', '2107-0180'], 'subject': [], 'container-title-short': 'Eur J Drug Metab Pharmacokinet', 'published': {'date-parts': [[2020, 8, 11]]}, 'assertion': [ { 'value': '11 August 2020', 'order': 1, 'name': 'first_online', 'label': 'First Online', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, {'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Declarations'}}, { 'value': 'No funding source.', 'order': 2, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Funding'}}, { 'value': 'The authors declare that they have no competing interest.', 'order': 3, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Conflict of interest'}}, { 'value': 'Not applicable.', 'order': 4, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Ethics approval'}}, { 'value': 'Not applicable.', 'order': 5, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Consent to participate'}}, { 'value': 'The authors have consent from their institutions.', 'order': 6, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Consent for publication'}}, { 'value': 'Not applicable.', 'order': 7, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Availability of data and material'}}, { 'value': 'Available at: ExternalRef removed.', 'order': 8, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Code availability'}}, { 'value': 'This content has been made available to all.', 'name': 'free', 'label': 'Free to read'}]}
Loading..
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
  or use drag and drop   
Submit