ABSTRACT
Background and objectives: The COVID-19 pandemic and its consequent severe acute respiratory syndrome (SARS) have taken the lives of millions since 2020. The use of neuraminidase inhibitors is a promising alternative in treating this disease, with several studies on off-label use being conducted since the beginning of the pandemic, but none of them have a large sample size and analyze multiple risk factors. The purpose of this article is to identify possible associations between various factors and risk of hospitalization, need for ventilation and death, as well as the influence of the prescription of Zanamivir and Oseltamivir on these same indicators. Methods: In this transversal study, approximately 900,000 medical records from all regions of Brazil were collected from the Ministry of Health database, and after that, proper statistical analysis of the variables was performed. Results: Hospitalization was associated with gender, ethnicity, education, local urbanization, State, and its percentage of elderly, as well as the climate. The prescription of Zanamivir and Oseltamivir was associated with higher incidence of symptoms, lower hospitalization and death rate, and lower need for invasive and non-invasive ventilation. Medical records from146,160 patients were excluded due to SARS not caused by COVID-19. Conclusion: From this data, it is possible to draw a risk profile for hospitalization by SARS and consider the use of Zanamivir and Oseltamivir as a treatment for these patients.(AU)
Justificativa e objetivos: A pandemia de COVID-19 e sua consequente síndrome respiratória aguda grave (SRAG) levaram milhões de pessoas a óbito desde 2020. O uso de inibidores da neuraminidase é uma alternativa promissora no tratamento dessa doença, com vários estudos sobre o uso off-label sendo conduzidos desde o início da pandemia, mas nenhum que tenha um grande tamanho amostral e que analise vários fatores de risco. O objetivo deste artigo é identificar possíveis associações entre diversos fatores e risco de hospitalização, necessidade de ventilação e óbito, assim como a influência da prescrição de Zanamivir e Oseltamivir nos mesmos indicadores. Métodos: Neste estudo transversal, foi feito o levantamento de aproximadamente 900 mil prontuários de todas as regiões do Brasil, provenientes de dados do Ministério da Saúde, e em seguida foi realizado o tratamento estatístico adequado das variáveis. Resultados: A hospitalização foi associada a sexo, etnia, escolaridade, urbanização do local, Estado e porcentagem de idosos do mesmo, assim como o clima. Já a prescrição de Zanamivir e Oseltamivir foi associada a maior incidência de sintomas, menor taxa de hospitalização e óbito e menor necessidade de ventilação invasiva e não-invasiva. Foram excluídos 146.160 prontuários devido a SRAG não ocasionada pela COVID-19. Conclusão: Com esses dados, é possível traçar um perfil de risco para hospitalização por SRAG e considerar o uso de Zanamivir e Oseltamivir como tratamento para esses pacientes.(AU)
Justificación y objetivos: la pandemia Covid-19 y su consiguiente síndrome respiratorio agudo severo (SRAS) han muerto millones de personas desde 2020. El uso de inhibidores de la neuraminidasa es una alternativa prometedora en el tratamiento de esta enfermedad, con varios estudios sobre el uso off-label que se realiza desde el principio de la pandemia, pero ninguno que tenga un tamaño de muestra grande y analice múltiples factores de riesgo. El propósito de este artículo es identificar posibles asociaciones entre varios factores y el riesgo de hospitalización, necesidad de ventilación y muerte, así como la influencia de la prescripción de Zanamivir y Oseltamivir en los mismos indicadores. Métodos: En este estudio transversal, se encuestaron a los datos del Ministerio de Salud de aproximadamente 900,000 registros de todas las regiones de Brasil, después de que se realizó un tratamiento estadístico adecuado de las variables. Resultados: La hospitalización se asoció con género, etnia, educación, urbanización del sitio, Estado y porcentaje de ancianos, así como el clima. La prescripción de zanamivir y oseltamivir se asoció con la mayor incidencia de síntomas, menor hospitalización y tasa de mortalidad y menor necesidad de ventilación invasiva y no invasiva. Se excluyeron 146,160 registros médicos debido a SRAS no causado por Covid-19. Conclusión: con estos datos, es posible dibujar un perfil de riesgo para la hospitalización por SRAS y considerar el uso de zanamivir y oseltamivir como tratamiento para estos pacientes.(AU)
Subject(s)
Humans , Severe Acute Respiratory Syndrome , Oseltamivir/therapeutic use , Zanamivir/therapeutic use , COVID-19 , Brazil , Cross-Sectional Studies , Risk FactorsABSTRACT
Influenza viruses exacerbate chronic obstructive pulmonary disease (COPD) with considerable morbidity and mortality. Zanamivir and oseltamivir are effective in treating influenza. However, their efficacy in relieving influenza symptoms in COPD patients remains unknown, with the lack of controlled trials in this subject. Therefore, we conducted this randomized controlled trial to investigate the clinical efficacy of both interventions in this population. Patients were allocated to two groups (80 patients each): oseltamivir (OSELTA) and zanamivir (ZANA) groups. Oseltamivir (75 mg) was orally administered twice daily for 5 days, while zanamivir (10 mg) was inhaled twice daily for 5 days. Clinical parameters including body temperature, influenza symptoms (i.e., sore throat, cough, etc.), and serial blood tests were recorded on days 1, 3, and 7. We analyzed primary (changes in body temperature) and secondary outcomes (changes in non-specific symptoms) using the pre-protocol and intention-to-treat analyses. Differences between groups were assessed using t-test. Oseltamivir and zanamivir significantly reduced body temperature on the 3rd day after treatment; however, the number of patients who reported clinical improvement in influenza-like symptoms was significantly higher in the OSELTA group compared to the ZANA group on days 3 (85 vs 68.8%, P=0.015) and 7 (97.5 vs 83.8%, P=0.003). However, no significant changes in hematological (white blood cells and its subtypes) and inflammatory (C-reactive protein) parameters were noted (P>0.05). Our results suggested that oseltamivir and zanamivir are effective in reducing body temperature, while oseltamivir led to better clinical improvement regarding influenza-like symptoms in patients with COPD.
Subject(s)
Humans , Male , Female , Middle Aged , Antiviral Agents/therapeutic use , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/drug therapy , Influenza, Human/drug therapy , Oseltamivir/therapeutic use , Zanamivir/therapeutic use , Enzyme Inhibitors/therapeutic use , NeuraminidaseABSTRACT
Antiviral drugs have significant action against influenza viruses A and B. Virus spread deadly disease in which many people die, and the country economy greatly suffer. Presently, most of the people need to get vaccination, which is depending on the dose limit in humans. It reacts directly or sometimes indirectly in the form of metabolites. However, it is mandatory to know how much drug is absorbed or metabolites concentration after administered. Therefore, pharmacokinetics data is very crucial for all drugs. Our review discusses the mechanism of drugs action and their activity and also describes how antiviral drugs and their metabolites is determined using a highly sensitive instrument such as high-performance liquid chromatography (HPLC), ultra-pressure liquid chromatography (UPLC), mass spectrometry (MS). Therefore, the present review gives brief information about antiviral drugs, their activity, biotransformation and analytical methods for quantification and this information will be helpful for any future studies done by experts in this field and will be beneficial for research scientists and influenza experts of all over the globe.
ABSTRACT
Influenza is caused by influenza virus.Neuraminidase inhibitors have produced certain effects for the management of influenza.Among them,Osehamivir has been in extensive use in adults and children,Peramivir and Zanamivir have been used in children.M2 inhibitors and traditional Chinese medicines can also be used in the management of influenza.In clinical practice,the physicians are expected to select anti-influenza drugs based on their mechanism of action and characteristics.
ABSTRACT
Influenza is caused by influenza virus.Neuraminidase inhibitors have produced certain effects for the management of influenza.Among them,Osehamivir has been in extensive use in adults and children,Peramivir and Zanamivir have been used in children.M2 inhibitors and traditional Chinese medicines can also be used in the management of influenza.In clinical practice,the physicians are expected to select anti-influenza drugs based on their mechanism of action and characteristics.
ABSTRACT
The objective of this study was to enhance the oral bioavailability (BA) of zanamivir (ZMR) by increasing its intestinal permeability using permeation enhancers (PE). Four different classes of PEs (Labrasol(R), sodium cholate, sodium caprate, hydroxypropyl beta-cyclodextrin) were investigated for their ability to enhance the permeation of ZMR across Caco-2 cell monolayers. The flux and Papp of ZMR in the presence of sodium caprate (SC) was significantly higher than other PEs in comparison to control, and was selected for further investigation. All concentrations of SC (10-200 mM) demonstrated enhanced flux of ZMR in comparison to control. The highest flux (13 folds higher than control) was achieved for the formulation with highest SC concentration (200 mM). The relative BA of ZMR formulation containing SC (PO-SC) in plasma at a dose of 10 mg/kg following oral administration in rats was 317.65% in comparison to control formulation (PO-C). Besides, the AUC0-24 h of ZMR in the lungs following oral administration of PO-SC was 125.22 +/- 27.25 ng hr ml(-1) with a Cmax of 156.00 +/- 24.00 ng/ml reached at 0.50+/-0.00 h. But, there was no ZMR detected in the lungs following administration of control formulation (PO-C). The findings of this study indicated that the oral formulation PO-SC containing ZMR and SC was able to enhance the BA of ZMR in plasma to an appropriate amount that would make ZMR available in lungs at a concentration higher (>10 ng/ml) than the IC50 concentration of influenza virus (0.64-7.9 ng/ml) to exert its therapeutic effect.
Subject(s)
Animals , Humans , Rats , Administration, Oral , Biological Availability , Caco-2 Cells , Influenza, Human , Inhibitory Concentration 50 , Lung , Orthomyxoviridae , Permeability , Plasma , Sodium , Sodium Cholate , ZanamivirABSTRACT
OBJECTIVE: To study the physicochemical property and stability of zanamivir dry powder inhalation (ZDI). METHODS: ZDI was prepared by spray-drying method. The hygroscopicity, relative humidity, particle size, powder morphology, emptying rate and deposition rate of the inhalation were determined. Water contents were analyzed by TGA. The stability of ZDI was determined by accelerated test and long-term test. RESULTS: The resultant powder inhalation exhibited the following properties: critical relative humidity was 67%, and average aerodynamic diameter dae was 90%, and deposition rate was >30% for thress batches of samples; the accelerated test and the long-term test indicated that zanamivir dry powder inhalation was stable. CONCLUSION: Zanamivir dry powder inhalation is stable and suitable for drug delivery.
ABSTRACT
Since the World Health Organization has officially declared a global influenza pandemic, the number of human cases of pandemic influenza A (H1N1) in 2009 has been increasing in many countries. Especially from mid-October, the number of domestic cases of influenza A (H1N1) has been exponentially increasing, with the number of confirmed cases reaching over 100,000. The clinical symptoms of novel influenza A (H1N1) include fever, cough, sore throat, runny nose, myalgia, headache, chills and fatigue. Nucleic acid amplification tests, including real time RT-PCR assay specific for 2009 novel influenza A (H1N1) can be used in the patients with suspected influenza. Antiviral treatment by using neuraminidase inhibitors (oseltamivir, zanamivir) is recommended by Centers for Disease Control and Prevention for treatment of novel influenza A (H1N1) disease. Personal and public efforts to control the outbreak of novel influenza A (H1N1) disease are required. Vaccination against pandemic H1N1 is important for personal health, but also to build community-level immunity to novel influenza A.
Subject(s)
Humans , Chills , Cough , Fatigue , Fever , Headache , Influenza, Human , Neuraminidase , Nose , Nucleic Acid Amplification Techniques , Oseltamivir , Pandemics , Pharyngitis , Vaccination , World Health Organization , ZanamivirABSTRACT
To investigate the emergence and prevalence of antiviral resistance, we analyzed influenza A/H3N2 viruses isolated in Korea during 2002/03 to 2003/04 season by genetic and phenotypic assay. For the genetic analysis to the amantadine, an M2 protein inhibitor, the M gene was amplified by RT-PCR and regions corresponding to the amino acid at positions 27, 30, and 31 were amplified by nested PCR with size of 154 bp, 95 bp, and 153 bp fragments, respectively. A total of 3 of 31 (9.7%) viruses were found to be mutated by restriction fragment length polymorphism (RFLP) with Sca I and sequence analysis, showing the single amino acid change (Ser to Asn) at position 31. Also it was observed that their growths in Madin-Darby Canine Kidney (MDCK) cells were unaffected by amantadine (up to 1 microgram/ml) in both plaque assay and WST-1 assay, confirming that these viruses were resistant against amantadine. We also examined the resistant pattern against zanamivir, a neuraminidase inhibitor, for 15 Korean influenza A/H3N2 viruses isolated in 2002~2003 season. Sequence analysis showed that there were no genetic changes of NA genes including R292K, K274Y, R152K, and E119V which were related to resistance against the neuraminidase inhibitor. In the NA inhibition assay to zanamivir, Korean isolates were found to be sensitive, ranging from 0.17 nM to 1.77 nM in 50% inhibitory concentration (IC(50)). These results suggest that monitoring for the antiviral resistance should be intensified and maintained to provide guideline for prophylaxis and treatment of influenza in Korea.
Subject(s)
Amantadine , Influenza, Human , Kidney , Korea , Neuraminidase , Orthomyxoviridae , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Prevalence , Seasons , Sequence Analysis , ZanamivirABSTRACT
BACKGROUND AND OBJECTIVES: This study aimed to investigate the differences in the morphologic changes of the nasal mucosa with influenza virus infection between zanamivir treated groups and non-treated group. MATERIALS AND METHOD: Zanamivir was administrated to the 15 rabbits before or after inoculation of the influenza viruses with time difference and 5 rabbits were inoculated the influenza viruses but not treated with zanamivir. The nasoturbinal mucosa was harvested and examined with the light microscope and electron microscope at 7th day after virus inoculation. RESULTS: The light microscopy results revealed that the total inflammatory scores were decreased in the zanamivir treated group. The electron microscopy results showed that the degree of ciliary loss, vacuolar degeneration of mitochondria and endoplasmic reticulum and rupture of cell membrane in the zanamivir treated group was less than those in the untreated group. The effects of inoculated zanamivir was related to the time of administration and best timing was immediate after inoculation of the influenza A virus. CONCLUSION: The use of zanamivir in the treatment of influenza A virus infection during the epidemic period is effective in controlling the inflammatory change.