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1.
Eur Rev Med Pharmacol Sci ; 25(1): 541-548, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33506946

RESUMO

OBJECTIVE: List the clinical data of the role of remdesivir in COVID-19, and try to make an objective evaluation and analyze its feasibility. MATERIALS AND METHODS: The keywords of "remdesivir", "COVID-19" and "SARS-CoV-2" were systematically searched in PubMed and Web of Science. After removing the repetitions, we summarize articles, letters, and comments on remdesivir in the treatment of COVID-19. RESULTS: In this review, we summarize clinical case of using remdesivir in the treatment of COVID-19, analyzed the final treatment results, and judged whether the drug was effective for the treatment of COVID-19. Also, attention was paid to the side effects of the drug. CONCLUSIONS: According to the clinical results, it was found that remdesivir was effective in the treatment of COVID-19. The drug has side effects, but the symptoms were mild and disappeared immediately after discontinuation of medication.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/uso terapêutico , /tratamento farmacológico , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/uso terapêutico , Alanina/administração & dosagem , Alanina/efeitos adversos , Alanina/uso terapêutico , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Humanos , Resultado do Tratamento
2.
BMJ Case Rep ; 13(10)2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33130588

RESUMO

An 82-year-old man with an extensive medical history presented to the emergency room with complaints of generalised weakness and cough. He tested positive for COVID-19 10 days prior to presenting to the emergency room. Although his symptoms started a week prior to diagnosis, his weakness increased, warranting emergency response. A comprehensive metabolic panel was drawn from the patient on admission, indicating markedly high liver function tests (LFTs) ≥20 times above the upper limit of normal. On day 1 of admission, the decision was still made to start remdesivir (5-day course) due to decompensated acute respiratory failure as well as dexamethasone. The patient's LFTs significantly improved throughout his hospital stay. The patient made a full recovery and was discharged on day 10 of hospitalisation.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Hepatopatias/diagnóstico , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , Insuficiência Respiratória/diagnóstico , Monofosfato de Adenosina/administração & dosagem , Idoso de 80 Anos ou mais , Alanina/administração & dosagem , Dexametasona/administração & dosagem , Serviço Hospitalar de Emergência , Humanos , Tempo de Internação , Hepatopatias/complicações , Testes de Função Hepática , Masculino , Pandemias/prevenção & controle , Pandemias/estatística & dados numéricos , Alta do Paciente , Insuficiência Respiratória/terapia , Índice de Gravidade de Doença , Resultado do Tratamento
3.
J Drugs Dermatol ; 19(9): 889-892, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-33026746

RESUMO

Early December 2019 witnessed an international outbreak of a novel coronavirus (COVID 19) designated severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). Since then, a number of therapeutic molecules have been explored to have potential efficacy against the SARS-Cov-2 per se or its sequelae. There are no Food and Drug Administration specific therapies approved so far; however, numerous drugs based on varying levels of evidence, in vitro studies and compassionate drug trials are being established as therapeutic agents, especially drugs approved for previous emergence of the severe acute respiratory syndrome (SARS-CoV-1) and Middle east respiratory syndrome coronavirus (MERS-Cov). Numerous active clinical trials for COVID-19 with more than 150 drugs and products are under study. Needless to say, many dermatological drugs are being employed to mitigate this pandemic threat. We aim to review drugs with potential against SARS-Cov-2 widely used in dermatology practice. Additionally, rampant and overzealous use of these drugs as well as introduction of new molecules might lead to emergence of adverse effects associated with these agents. Dermatologists must be on lookout for any cutaneous adverse effects of these drugs. J Drugs Dermatol. 2020;19(9):889-892. doi:10.36849/JDD.2020.5323.


Assuntos
Antivirais/efeitos adversos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Fármacos Dermatológicos/efeitos adversos , Erupção por Droga/etiologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/análogos & derivados , Alanina/administração & dosagem , Alanina/efeitos adversos , Alanina/análogos & derivados , Antivirais/uso terapêutico , Produtos Biológicos/administração & dosagem , Produtos Biológicos/efeitos adversos , Fármacos Dermatológicos/uso terapêutico , Erupção por Droga/epidemiologia , Erupção por Droga/fisiopatologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Incidência , Masculino , Pandemias , Prognóstico , Medição de Risco , Síndrome Respiratória Aguda Grave/diagnóstico , Síndrome Respiratória Aguda Grave/epidemiologia
4.
Clin Med (Lond) ; 20(6): e215-e217, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32863273

RESUMO

The emergence of the novel beta coronavirus SARS-CoV-2 and the ensuing COVID-19 pandemic has generated a rapidly evolving research landscape in the search for new therapeutic agents. The intravenous antiviral drug remdesivir has in vitro activity against SARS-CoV-2 and now studies have reported its clinical efficacy, demonstrating shorter time to recovery in hospitalised patients with severe COVID-19. Adverse event rates were low and remdesivir has now received conditional marketing authorisation from the European Medicines Agency. An interim clinical commissioning policy is in place in the UK. These studies make remdesivir the first antiviral drug able to alter the natural history of severe COVID-19, and a benchmark for the comparison of new therapies in the future. Ongoing studies are investigating its use in early mild/moderate COVID-19, alternative formulations, and the combination of remdesivir with immunomodulatory agents.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/uso terapêutico , Administração Intravenosa , Alanina/administração & dosagem , Alanina/efeitos adversos , Alanina/uso terapêutico , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Betacoronavirus , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Antimicrob Agents Chemother ; 64(11)2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-32868327

RESUMO

Remdesivir has reported efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro and in vivo Drug-drug interactions limit therapeutic options in transplant patients. Remdesivir and its metabolite GS-441524 are excreted principally in urine. In intensive care unit (ICU) settings, in which multiple-organ dysfunctions can occur rapidly, hemodialysis may be a viable option for maintaining remdesivir treatment, while improving tolerance, by removing both remdesivir's metabolite (GS-441524) and sulfobutylether ß-cyclodextrin sodium (SEBCD). Additional studies may prove informative, particularly in the evaluations of therapeutic options for coronavirus disease 2019 (COVID-19).


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/administração & dosagem , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/terapia , Furanos/urina , Pneumonia Viral/terapia , Pirróis/urina , Triazinas/urina , beta-Ciclodextrinas/urina , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/química , Monofosfato de Adenosina/metabolismo , Alanina/administração & dosagem , Alanina/efeitos adversos , Alanina/química , Alanina/metabolismo , Antivirais/efeitos adversos , Antivirais/química , Antivirais/metabolismo , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/cirurgia , Infecções por Coronavirus/virologia , Interações Medicamentosas , Furanos/efeitos adversos , Furanos/química , Humanos , Unidades de Terapia Intensiva , Transplante de Pulmão , Insuficiência de Múltiplos Órgãos , Pandemias , Pneumonia Viral/cirurgia , Pneumonia Viral/virologia , Pirróis/efeitos adversos , Pirróis/química , Diálise Renal , Transplantados , Triazinas/efeitos adversos , Triazinas/química , beta-Ciclodextrinas/efeitos adversos , beta-Ciclodextrinas/química
6.
Expert Opin Investig Drugs ; 29(11): 1195-1198, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32896184

RESUMO

INTRODUCTION: In clinical trial for the Ebola virus, the broad-spectrum anti-viral agent remdesivir was shown to have a good safety profile. Remdesivir is now being tested in severe COVID-19. AREAS COVERED: The Gilead Sciences SIMPLE trial suggests that the short-term use of remdesivir probably does not increase mortality dramatically or have serious short-term toxicity when used to treat severe COVID-19. The Adaptive COVID-19 treatment trials (ACTT1) trial showed that remdesivir may shorten recovery and decrease mortality in severe COVID-19 without increasing adverse effects. EXPERT OPINION: It seems to me that we have learnt very little from the SIMPLE trial, and this would be predicted from a trial that has no control or placebo group. The results of ACTT1 were reported early after an interim analysis showed that a higher than expected number of recoveries had occurred. There was an indication that remdesivir may be reducing mortality, but this was no statistical significance. The trial is continuing, and the final data are eagerly awaited to determine whether remdesivir is a game-changing remedy or a ripple in the ongoing search for a medicine for the treatment of COVID-19.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Alanina/administração & dosagem , Alanina/efeitos adversos , Antivirais/efeitos adversos , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Humanos , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Resultado do Tratamento
8.
Emerg Med J ; 37(8): 522-523, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32753375

RESUMO

A short-cut review of the available medical literature was carried out to establish whether remdesivir was an effective treatment for patients with confirmed COVID-19 infection. After abstract review, five papers were found to answer this clinical question using the detailed search strategy. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. It is concluded that despite some recent promising studies, further well-designed and larger trials are needed to answer this specific question.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Adulto , Alanina/administração & dosagem , Alanina/efeitos adversos , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/isolamento & purificação , Ensaios Clínicos como Assunto , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/fisiopatologia , Prática Clínica Baseada em Evidências , Feminino , Humanos , Masculino , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/etiologia , Pneumonia Viral/fisiopatologia , Resultado do Tratamento
9.
Eur J Clin Invest ; 50(11): e13383, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32810285

RESUMO

BACKGROUND: Several therapeutic agents have been investigated for treatment of novel coronavirus 2019 (nCOV-2019). We conducted a systematic review and meta-analysis to assess the efficacy of various treatment modalities in nCOV-2019 patients. METHODS: A literature search was conducted before 29 June 2020 in PubMed, Google Scholar and Cochrane library databases. A fixed-effect model was applied if I2  < 50%, else results were combined using random-effect model. Risk ratio (RR) or standardized mean difference (SMD) along with 95% confidence interval (95% CI) was used to pool the results. Between-study heterogeneity was explored using influence and sensitivity analyses, and publication bias was assessed using funnel plots. Entire statistical analysis was conducted in R version 3.6.2. RESULTS: Fifty studies involving 15 in vitro and 35 clinical studies including 9170 nCOV-2019 patients were included. Lopinavir-ritonavir was significantly associated with shorter mean time to clinical recovery (SMD -0.32; 95% CI -0.57 to -0.06), remdesivir was significantly associated with better overall clinical recovery (RR 1.17; 95% CI 1.07 to 1.29), and tocilizumab was associated with less all-cause mortality (RR 0.38; 95% CI 0.16 to 0.93). Hydroxychloroquine was associated with longer time to clinical recovery and less overall clinical recovery. It additionally had higher all-cause mortality and more total adverse events. CONCLUSION: Our meta-analysis suggests that except in vitro studies, no treatment has shown overall favourable outcomes in nCOV-2019 patients. Lopinavir-ritonavir, remdesivir and tocilizumab may have some benefits, while hydroxychloroquine administration may cause harm in nCOV-2019 patients. Results from upcoming large clinical trials may further clarify role of these drugs.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/análogos & derivados , Alanina/administração & dosagem , Alanina/análogos & derivados , Anticorpos Monoclonais Humanizados/administração & dosagem , Infecções por Coronavirus/diagnóstico , Europa (Continente) , Feminino , Humanos , Lopinavir/administração & dosagem , Masculino , Pandemias/prevenção & controle , Pandemias/estatística & dados numéricos , Pneumonia Viral/diagnóstico , Prognóstico , Ritonavir/administração & dosagem , Análise de Sobrevida , Resultado do Tratamento
10.
JAMA ; 324(11): 1048-1057, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32821939

RESUMO

Importance: Remdesivir demonstrated clinical benefit in a placebo-controlled trial in patients with severe coronavirus disease 2019 (COVID-19), but its effect in patients with moderate disease is unknown. Objective: To determine the efficacy of 5 or 10 days of remdesivir treatment compared with standard care on clinical status on day 11 after initiation of treatment. Design, Setting, and Participants: Randomized, open-label trial of hospitalized patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and moderate COVID-19 pneumonia (pulmonary infiltrates and room-air oxygen saturation >94%) enrolled from March 15 through April 18, 2020, at 105 hospitals in the United States, Europe, and Asia. The date of final follow-up was May 20, 2020. Interventions: Patients were randomized in a 1:1:1 ratio to receive a 10-day course of remdesivir (n = 197), a 5-day course of remdesivir (n = 199), or standard care (n = 200). Remdesivir was dosed intravenously at 200 mg on day 1 followed by 100 mg/d. Main Outcomes and Measures: The primary end point was clinical status on day 11 on a 7-point ordinal scale ranging from death (category 1) to discharged (category 7). Differences between remdesivir treatment groups and standard care were calculated using proportional odds models and expressed as odds ratios. An odds ratio greater than 1 indicates difference in clinical status distribution toward category 7 for the remdesivir group vs the standard care group. Results: Among 596 patients who were randomized, 584 began the study and received remdesivir or continued standard care (median age, 57 [interquartile range, 46-66] years; 227 [39%] women; 56% had cardiovascular disease, 42% hypertension, and 40% diabetes), and 533 (91%) completed the trial. Median length of treatment was 5 days for patients in the 5-day remdesivir group and 6 days for patients in the 10-day remdesivir group. On day 11, patients in the 5-day remdesivir group had statistically significantly higher odds of a better clinical status distribution than those receiving standard care (odds ratio, 1.65; 95% CI, 1.09-2.48; P = .02). The clinical status distribution on day 11 between the 10-day remdesivir and standard care groups was not significantly different (P = .18 by Wilcoxon rank sum test). By day 28, 9 patients had died: 2 (1%) in the 5-day remdesivir group, 3 (2%) in the 10-day remdesivir group, and 4 (2%) in the standard care group. Nausea (10% vs 3%), hypokalemia (6% vs 2%), and headache (5% vs 3%) were more frequent among remdesivir-treated patients compared with standard care. Conclusions and Relevance: Among patients with moderate COVID-19, those randomized to a 10-day course of remdesivir did not have a statistically significant difference in clinical status compared with standard care at 11 days after initiation of treatment. Patients randomized to a 5-day course of remdesivir had a statistically significant difference in clinical status compared with standard care, but the difference was of uncertain clinical importance. Trial Registration: ClinicalTrials.gov Identifier: NCT04292730.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/uso terapêutico , Administração Intravenosa , Idoso , Alanina/administração & dosagem , Alanina/efeitos adversos , Alanina/uso terapêutico , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Infecções por Coronavirus/mortalidade , Esquema de Medicação , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pandemias , Gravidade do Paciente , Pneumonia Viral/mortalidade , Resultado do Tratamento
11.
Pharmazie ; 75(8): 407-410, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32758342

RESUMO

New drugs against the in COVID-19 pandemic are urgently needed. Gilead Science's remdesivir has been introduced to China through special approval procedures, and was directly conducting the Phase III clinical trial. As expected, the marketing authorization process was completed soon. The drug brought hope to patients as well as business opportunities to companies. However, we must pay attention to the patent competition, generic drug competition and other unfair competition that remdesivir may face in China. China also needs to strengthen the innovation ability and international cooperation ability of local pharmaceutical companies by taking advantages of the opportunity to introduce remdesivir.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/economia , Alanina/administração & dosagem , Alanina/economia , Antivirais/economia , China , Ensaios Clínicos como Assunto , Infecções por Coronavirus/epidemiologia , Aprovação de Drogas , Indústria Farmacêutica/economia , Medicamentos Genéricos/administração & dosagem , Medicamentos Genéricos/economia , Competição Econômica , Humanos , Pandemias , Pneumonia Viral/epidemiologia
12.
Hepatol Int ; 14(5): 881-883, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32725454
13.
West J Emerg Med ; 21(4): 737-741, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32726230

RESUMO

In March 2020, the World Health Organization declared the spread of SARS-CoV-2 a global pandemic. To date, coronavirus disease-2019 (COVID-19) has spread to over 200 countries, leading to over 1.6 million cases and over 99,000 deaths. Given that there is neither a vaccine nor proven treatment for COVID-19, there is currently an urgent need for effective pharmacotherapy. To address the need for an effective treatment of SARS-CoV-2 during the worldwide pandemic, this systematic review of intravenous (IV) remdesivir was performed. Remdesivir, an anti-viral prodrug originally developed to treat Ebola virus disease, has shown broad spectrum activity against the Coronavirus family. A recent case report reported improvement of clinical symptoms with remdesivir in a patient with COVID-19. After conducting a systematic search of 18 clinical trial registries and three large scientific databases, we identified 86 potentially eligible items. Following removal of duplicates (n = 21), eligible studies were reviewed independently by two authors. After the first round of screening, inter-rater agreement was 98.5% (κ = 0.925). After the second round of full-text screening, inter-rater agreement was 100%. A total of seven ongoing and recruiting clinical trials of remdesivir (100-200 milligrams, intravenous [IV]) were included. We identified the following primary outcomes: patients discharged (n = 2); time to clinical status improvement (n = 2); improved O2 saturation (n = 2); body temperature normalization (n = 2); and clinical status (n = 1). Secondary outcomes in all identified studies included documentation of adverse events. Phase 3 trials are expected to be completed between April 2020-2023. Therefore, despite supportive data from in vitro and in vivo studies, the clinical effectiveness of IV remdesivir for treatment of COVID-19 and potential side effects remain incompletely defined in the human population.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/uso terapêutico , Administração Intravenosa , Alanina/administração & dosagem , Alanina/uso terapêutico , Antivirais/administração & dosagem , Ensaios Clínicos como Assunto , Humanos , Pandemias , Resultado do Tratamento
15.
Obstet Gynecol ; 136(5): 1025-1029, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32618794

RESUMO

BACKGROUND: There are limited data regarding treatment options for pregnant women with severe coronavirus disease 2019 (COVID-19). CASE: A 35-year-old primigravid patient at 22 weeks of gestation presented with 7 days of fever, cough, anosmia, and dyspnea. Nasopharyngeal swab was positive for the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and a chest X-ray demonstrated bilateral patchy infiltrates. Laboratory evaluation was notable for marked elevation of interleukin-6 and C-reactive protein concentrations. On hospital day 3, owing to increased dyspnea and oxygen requirement, the patient was treated with tocilizumab followed by 5 days of remdesivir. She responded well, recovered to room air, and was discharged home after a 9-day hospitalization. CONCLUSION: Tocilizumab and remdesivir may be effective for treatment of severe COVID-19 in pregnancy, but additional data are needed to guide risk-benefit considerations.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Anticorpos Monoclonais Humanizados/administração & dosagem , Infecções por Coronavirus , Pulmão/diagnóstico por imagem , Pandemias , Pneumonia Viral , Complicações Infecciosas na Gravidez , Monofosfato de Adenosina/administração & dosagem , Adulto , Alanina/administração & dosagem , Antivirais/administração & dosagem , Betacoronavirus/isolamento & purificação , Proteína C-Reativa/análise , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/fisiopatologia , Feminino , Humanos , Interleucina-6/sangue , Oximetria/métodos , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/etiologia , Pneumonia Viral/fisiopatologia , Gravidez , Complicações Infecciosas na Gravidez/sangue , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Radiografia Torácica/métodos , Resultado do Tratamento
16.
Drug Discov Ther ; 14(3): 109-116, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32669519

RESUMO

With the emergence of coronavirus disease 2019 (COVID-19) in late December 2019, many clinical studies on a group of the pre-existing medications have been conducted to treat this disease. The purpose of this review was to compile the clinical evidences on the use of the pre-existing medications and potential therapeutic options for the management of COVID-19. We reviewed the literature to highlight the clinical studies on the use of these medications to be available as a scientific overview for further perspectives. Inadequate clinical evidences are available to be affirmed for the repurposing of old medications, and large scale clinical studies are needed to be carried out to further confirm the use of these agents. The clinical use of these medications should be well explained and follow the framework of Monitored Emergency use of Unregistered Interventions (MEURI) of World Health Organization (WHO).


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/administração & dosagem , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Reposicionamento de Medicamentos/métodos , Hidroxicloroquina/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/administração & dosagem , Alanina/administração & dosagem , Antirreumáticos/administração & dosagem , Betacoronavirus/metabolismo , Ensaios Clínicos como Assunto/métodos , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Reposicionamento de Medicamentos/tendências , Humanos , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico
17.
J Allergy Clin Immunol ; 146(4): 786-789, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32710973

Assuntos
Antivirais/efeitos adversos , Infecções por Coronavirus/tratamento farmacológico , Síndrome da Liberação de Citocina/prevenção & controle , Hipersensibilidade a Drogas/etiologia , Fatores Imunológicos/efeitos adversos , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/análogos & derivados , Corticosteroides/uso terapêutico , Alanina/administração & dosagem , Alanina/efeitos adversos , Alanina/análogos & derivados , Amidas/administração & dosagem , Amidas/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Antivirais/administração & dosagem , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/virologia , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/tratamento farmacológico , Hipersensibilidade a Drogas/imunologia , Humanos , Imunidade Inata/efeitos dos fármacos , Fatores Imunológicos/administração & dosagem , Indóis/administração & dosagem , Indóis/efeitos adversos , Infliximab/administração & dosagem , Infliximab/efeitos adversos , Proteína Antagonista do Receptor de Interleucina 1/administração & dosagem , Proteína Antagonista do Receptor de Interleucina 1/efeitos adversos , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Pirazinas/administração & dosagem , Pirazinas/efeitos adversos , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Índice de Gravidade de Doença
18.
ACS Chem Neurosci ; 11(15): 2137-2144, 2020 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-32639711

RESUMO

Now, it has been evidenced that Covid19 (SARS-CoV-2) infects the brain tissues. Along with this, a challenge has been raised for research professionals to find effective drugs for its treatment since the recent spread of this virus from Wuhan, China. Targeting the treatment of brain infection, it has also been a challenge that the clinical drug should have good CNS penetration ability to cross the blood-brain barrier.


Assuntos
Betacoronavirus , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/metabolismo , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/metabolismo , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/metabolismo , Alanina/administração & dosagem , Alanina/análogos & derivados , Alanina/metabolismo , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/metabolismo , Antivirais/administração & dosagem , Antivirais/metabolismo , Betacoronavirus/efeitos dos fármacos , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/virologia , Encéfalo/efeitos dos fármacos , Fármacos do Sistema Nervoso Central/administração & dosagem , Fármacos do Sistema Nervoso Central/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Metilprednisolona/administração & dosagem , Metilprednisolona/metabolismo , Pandemias , Resultado do Tratamento
19.
J Nanosci Nanotechnol ; 20(12): 7311-7323, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32711596

RESUMO

We started a study on the molecular docking of six potential pharmacologically active inhibitors compounds that can be used clinically against the COVID-19 virus, in this case, remdesivir, ribavirin, favipiravir, galidesivir, hydroxychloroquine and chloroquine interacting with the main COVID-19 protease in complex with a COVID-19 N3 protease inhibitor. The highest values of affinity energy found in order from highest to lowest were chloroquine (CHL), hydroxychloroquine (HYC), favipiravir (FAV), galidesivir (GAL), remdesivir (REM) and ribavirin (RIB). The possible formation of hydrogen bonds, associations through London forces and permanent electric dipole were analyzed. The values of affinity energy obtained for the hydroxychloroquine ligands was -9.9 kcal/mol and for the chloroquine of -10.8 kcal/mol which indicate that the coupling contributes to an effective improvement of the affinity energies with the protease. Indicating that, the position chosen to make the substitutions may be a pharmacophoric group, and cause changes in the protease.


Assuntos
Antivirais/química , Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/enzimologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Cisteína Endopeptidases/química , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Inibidores de Proteases/química , Inibidores de Proteases/farmacologia , Proteínas não Estruturais Virais/antagonistas & inibidores , Proteínas não Estruturais Virais/química , Adenina/administração & dosagem , Adenina/análogos & derivados , Adenina/química , Adenina/farmacologia , Adenosina/análogos & derivados , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/química , Monofosfato de Adenosina/farmacologia , Alanina/administração & dosagem , Alanina/análogos & derivados , Alanina/química , Alanina/farmacologia , Amidas/administração & dosagem , Amidas/química , Amidas/farmacologia , Antivirais/administração & dosagem , Sítios de Ligação , Cloroquina/administração & dosagem , Cloroquina/química , Cloroquina/farmacologia , Interações Medicamentosas , Humanos , Ligação de Hidrogênio , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/química , Hidroxicloroquina/farmacologia , Ligantes , Simulação de Acoplamento Molecular , Nanotecnologia , Pandemias , Inibidores de Proteases/administração & dosagem , Pirazinas/administração & dosagem , Pirazinas/química , Pirazinas/farmacologia , Pirrolidinas/administração & dosagem , Pirrolidinas/química , Pirrolidinas/farmacologia , Ribavirina/administração & dosagem , Ribavirina/química , Ribavirina/farmacologia , Eletricidade Estática
20.
JAMA Pediatr ; 174(10): e202422, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32501511

RESUMO

Importance: Children of all ages appear susceptible to severe acute respiratory syndrome coronavirus 2 infection. To support pediatric clinical studies for investigational treatments of coronavirus disease 2019 (COVID-19), pediatric-specific dosing is required. Objective: To define pediatric-specific dosing regimens for hydroxychloroquine and remdesivir for COVID-19 treatment. Design, Setting, and Participants: Pharmacokinetic modeling and simulation were used to extrapolate investigated adult dosages toward children (March 2020-April 2020). Physiologically based pharmacokinetic modeling was used to inform pediatric dosing for hydroxychloroquine. For remdesivir, pediatric dosages were derived using allometric-scaling with age-dependent exponents. Dosing simulations were conducted using simulated pediatric and adult participants based on the demographics of a white US population. Interventions: Simulated drug exposures following a 5-day course of hydroxychloroquine (400 mg every 12 hours × 2 doses followed by 200 mg every 12 hours × 8 doses) and a single 200-mg intravenous dose of remdesivir were computed for simulated adult participants. A simulation-based dose-ranging study was conducted in simulated children exploring different absolute and weight-normalized dosing strategies. Main Outcomes and Measures: The primary outcome for hydroxychloroquine was average unbound plasma concentrations for 5 treatment days. Additionally, unbound interstitial lung concentrations were simulated. For remdesivir, the primary outcome was plasma exposure (area under the curve, 0 to infinity) following single-dose administration. Results: For hydroxychloroquine, the physiologically based pharmacokinetic model analysis included 500 and 600 simulated white adult and pediatric participants, respectively, and supported weight-normalized dosing for children weighing less than 50 kg. Geometric mean-simulated average unbound plasma concentration values among children within different developmental age groups (32-35 ng/mL) were congruent to adults (32 ng/mL). Simulated unbound hydroxychloroquine concentrations in lung interstitial fluid mirrored those in unbound plasma and were notably lower than in vitro concentrations needed to mediate antiviral activity. For remdesivir, the analysis included 1000 and 6000 simulated adult and pediatric participants, respectively. The proposed pediatric dosing strategy supported weight-normalized dosing for participants weighing less than 60 kg. Geometric mean-simulated plasma area under the time curve 0 to infinity values among children within different developmental age-groups (4315-5027 ng × h/mL) were similar to adults (4398 ng × h/mL). Conclusions and Relevance: This analysis provides pediatric-specific dosing suggestions for hydroxychloroquine and remdesivir and raises concerns regarding hydroxychloroquine use for COVID-19 treatment because concentrations were less than those needed to mediate an antiviral effect.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/administração & dosagem , Antivirais/farmacocinética , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/farmacocinética , Pneumonia Viral/tratamento farmacológico , Terapias em Estudo/métodos , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/farmacocinética , Adolescente , Adulto , Alanina/administração & dosagem , Alanina/farmacocinética , Criança , Pré-Escolar , Esquema de Medicação , Cálculos da Dosagem de Medicamento , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Modelos Biológicos , Pandemias , Simulação de Paciente , Adulto Jovem
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