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Viruses Nov 2023Influenza can cause respiratory infections, leading to significant morbidity and mortality in humans. While current influenza vaccines offer varying levels of...
Influenza can cause respiratory infections, leading to significant morbidity and mortality in humans. While current influenza vaccines offer varying levels of protection, there remains a pressing need for effective antiviral drugs to supplement vaccine efforts. Currently, the FDA-approved antiviral drugs for influenza include oseltamivir, zanamivir, peramivir, and baloxavir marboxil. These antivirals primarily target the virus, making them vulnerable to drug resistance. In this study, we evaluated the efficacy of the neuraminidase inhibitor, oseltamivir, against probenecid, which targets the host cells and is less likely to engender resistance. Our results show that probenecid has superior antiviral efficacy compared to oseltamivir in both in vitro replication assays and in vivo mouse models of influenza infection.
Topics: Humans; Animals; Mice; Oseltamivir; Influenza, Human; Probenecid; Influenza Vaccines; Antiviral Agents; Enzyme Inhibitors; Virus Replication; Neuraminidase; Drug Resistance, Viral
PubMed: 38140606
DOI: 10.3390/v15122366 -
Virus Research Mar 2021Coronavirus disease 19 (COVID-19) has posed serious threats to the general population. To relieve the crisis, a comparison of drug effects against COVID-19 is... (Comparative Study)
Comparative Study
Coronavirus disease 19 (COVID-19) has posed serious threats to the general population. To relieve the crisis, a comparison of drug effects against COVID-19 is instructive. Between January 27, 2020 and March 21, 2020, a total of 333 patients treated with arbidol, corticosteroids, hydroxychloroquine, lopinavir/ritonavir, or oseltamivir monotherapy, having definite outcomes and serological antibody detection results, were retrospectively analyzed. The hydroxychloroquine group had a significantly reduced duration of hospital stay than the arbidol and corticosteroids groups. The oseltamivir group had a significantly shorter length of hospital stay than the arbidol, corticosteroids, and lopinavir/ritonavir groups. The hydroxychloroquine group had a significantly higher IgM titer than the other four groups and exhibited significantly higher IgG levels than the arbidol, lopinavir/ritonavir, and oseltamivir groups. Our findings indicated that hydroxychloroquine might have the potential for efficient COVID-19 management, while oseltamivir should be prudently considered in combination therapy.
Topics: Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Antibodies, Viral; COVID-19; Drug Combinations; Female; Humans; Hydroxychloroquine; Immunoglobulin G; Immunoglobulin M; Indoles; Length of Stay; Lopinavir; Male; Middle Aged; Oseltamivir; Retrospective Studies; Ritonavir; SARS-CoV-2; Young Adult; COVID-19 Drug Treatment
PubMed: 33333102
DOI: 10.1016/j.virusres.2020.198262 -
Pharmacological Reports : PR Dec 2021The global spread of COVID-19 has imparted significant economic, medical, and social burdens. Like adults, children are affected by this pandemic. However, milder... (Review)
Review
The global spread of COVID-19 has imparted significant economic, medical, and social burdens. Like adults, children are affected by this pandemic. However, milder clinical symptoms are often experienced by them. Only a minimal proportion of the affected patients may develop severe and complicated COVID-19. Supportive treatment is recommended in all patients. Antiviral and immunomodulatory medications are spared for hospitalized children with respiratory distress or severe to critical disease. Up till now, remdesivir is the only USFDA-approved anti-COVID-19 medication indicated in the majority of symptomatic patients with moderate to severe disease. Dexamethasone is solely recommended in patients with respiratory distress maintained on oxygen or ventilatory support. The use of these medications in pediatric patients is founded on evidence deriving from adult studies. No randomized controlled trials (RCTs) involving pediatric COVID-19 patients have assessed these medications' efficacy and safety, among others. Similarly, three novel monoclonal anti-SARS-CoV-2 spike protein antibodies, bamlanivimab, casirivimab and imdevimab, have been recently authorized by the USFDA. Nonetheless, their efficacy has not been demonstrated by multiple RCTs. In this review, we aim to dissect the various potential therapeutics used in children with COVID-19. We aspire to provide a comprehensive review of the available evidence and display the mechanisms of action and the pharmacokinetic properties of the studied therapeutics. Our review offers an efficient and practical guide for treating children with COVID-19.
Topics: Adenosine Monophosphate; Alanine; Anti-Inflammatory Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antiviral Agents; Azithromycin; Child; Dexamethasone; Humans; Hydroxychloroquine; Ivermectin; Lopinavir; Oseltamivir; SARS-CoV-2; Spike Glycoprotein, Coronavirus; COVID-19 Drug Treatment
PubMed: 34458951
DOI: 10.1007/s43440-021-00316-1 -
Regulatory Toxicology and Pharmacology... Apr 2020Oseltamivir is an antiviral drug approved to treat influenza in humans. Although the dosing regimen of this drug is well established for non-pregnant patients, it is not...
Oseltamivir is an antiviral drug approved to treat influenza in humans. Although the dosing regimen of this drug is well established for non-pregnant patients, it is not clear if the significant physiological alterations associated with pregnancy affect the pharmacokinetics of oseltamivir and, thus, warrant different dosing regimens to assure efficacy. In this study, we investigated the suitability of rhesus macaques as an animal model for studying oseltamivir pharmacokinetics during all trimesters of pregnancy in comparison to pre-pregnant conditions. Specifically, we compared the pharmacokinetics of oseltamivir and its pharmacologically active metabolite oseltamivir carboxylate in rhesus monkeys after intravenous and nasogastric administration of 2.5 mg oseltamivir phosphate/kg body weight given prior to and during the first, second, and third trimesters of pregnancy. Pregnancy had only a modest effect upon the pharmacokinetic parameters of oseltamivir and oseltamivir carboxylate. Monkeys treated intravenously in the third trimester had a reduction in Vd and CL, compared to non-pregnant monkeys. These changes did not occur in the other two trimesters. Pregnant monkeys treated intravenously had 20-25% decrease in AUC of oseltamivir carboxylate and a corresponding increase in Vd and CL. Pregnant monkeys treated nasogastrically with oseltamivir phosphate demonstrated a pattern that recapitulated intravenous dosing. Taken together these data indicate that rhesus monkeys are an acceptable model for studying drug-pregnancy interactions.
Topics: Animals; Antiviral Agents; Dose-Response Relationship, Drug; Female; Injections, Intravenous; Intubation, Gastrointestinal; Macaca mulatta; Molecular Conformation; Oseltamivir; Phosphorous Acids; Pregnancy
PubMed: 31927005
DOI: 10.1016/j.yrtph.2019.104569 -
The American Journal of Managed Care Mar 2022To determine whether baloxavir use is associated with lower health care resource utilization (HCRU) and costs for secondary influenza complications post treatment...
OBJECTIVES
To determine whether baloxavir use is associated with lower health care resource utilization (HCRU) and costs for secondary influenza complications post treatment compared with oseltamivir.
STUDY DESIGN
Retrospective cohort study.
METHODS
Patients filling a prescription for baloxavir or oseltamivir within 48 hours following an influenza-related outpatient visit were identified in the 2018-2019 influenza season from the US Truven MarketScan Research Databases and propensity matched 1:2 (baloxavir:oseltamivir). Outcomes were assessed 15 and 30 days after antiviral treatment and included all-cause, all respiratory-related, and select respiratory-related (influenza, asthma, chronic obstructive pulmonary disease, or infection) HCRU and costs.
RESULTS
The study included 5080 baloxavir-treated and 10,160 matched oseltamivir-treated patients. All-cause emergency department (ED) visits and inpatient hospitalizations were lower in baloxavir-treated patients, with a statistically significant difference in the percentage hospitalized at 30 days (0.3% vs 0.5%; P = .04). ED visits for all or select respiratory-related conditions were significantly reduced with baloxavir (P < .01 for all comparisons). Mean per-patient cost savings at day 30 for all-cause, all respiratory-related, and select respiratory-related conditions were $79, $50, and $51, respectively, despite slightly higher prescription costs for baloxavir. In high-risk patients (baloxavir: n = 1958; oseltamivir: n = 3949), the incidence of ED visits was significantly lower for all respiratory-related and select respiratory-related conditions (P < .01); cost savings with baloxavir in the high-risk cohort were substantially greater than in the overall cohort.
CONCLUSIONS
Treatment of patients with influenza with single-dose baloxavir was generally associated with lower HCRU and costs post treatment compared with oseltamivir, particularly in high-risk patients.
Topics: Antiviral Agents; Dibenzothiepins; Humans; Influenza, Human; Morpholines; Oseltamivir; Pyridones; Retrospective Studies; Triazines
PubMed: 35404552
DOI: 10.37765/ajmc.2022.88786 -
Antiviral Research Aug 2023Our previous study shows favipiravir and oseltamivir combination therapy may accelerate clinical recovery compared to oseltamivir monotherapy in severe influenza, but...
Our previous study shows favipiravir and oseltamivir combination therapy may accelerate clinical recovery compared to oseltamivir monotherapy in severe influenza, but its effect on virological evolution and resistance mutation against oseltamivir is still unknown. In this study, we collected longitudinal respiratory samples from influenza patients who underwent combination therapy and applied them to next generation sequencing of the whole genome of the influenza A virus (IAV). We also included a cohort untreated with any antivirals to serve as the control. In total, 62 samples from 19 patients treated with combination therapy and 20 samples from 20 patients untreated were successfully sequenced. The nucleotide diversity in the whole genome of IAV in the combination group showed no difference compared to that in the control group (P > 0.05). Moreover, we observed 174 kinds of nonsynonymous nucleotide substitutions in patients with combination therapy, mostly in NA (n = 44) and HA (n = 43). Of them, the G→A transition was the dominant variant type (27%) and 46/174 (26%) was reported to have biological effects, such as increased pathogenicity and polymerase activity. Among the 29 mutations conferring reduction in oseltamivir sensitivity we investigated, H275Y was the only mutation detected in the 4 samples from 1 of 19 patients and demonstrated increasing frequency during the treatment. Mutations conferring favipiravir resistance were not observed. Our studies showed combination therapy of favipiravir and oseltamivir has little effect on virus nucleotide diversity, nor prevents the increase of oseltamivir-resistant variants.
Topics: Humans; Oseltamivir; Influenza, Human; Influenza A virus; Influenza A Virus, H1N1 Subtype; Drug Resistance, Viral; Antiviral Agents; Neuraminidase
PubMed: 37369282
DOI: 10.1016/j.antiviral.2023.105657 -
Antiviral Research Apr 2022Global analysis of the susceptibility of influenza viruses to neuraminidase (NA) inhibitors (NAIs) and the polymerase acidic (PA) inhibitor (PAI) baloxavir was conducted... (Review)
Review
Global analysis of the susceptibility of influenza viruses to neuraminidase (NA) inhibitors (NAIs) and the polymerase acidic (PA) inhibitor (PAI) baloxavir was conducted by five World Health Organization Collaborating Centres for Reference and Research on Influenza during two periods (May 2018-May 2019 and May 2019-May 2020). Combined phenotypic and NA sequence-based analysis revealed that the global frequency of viruses displaying reduced or highly reduced inhibition (RI or HRI) or potential to show RI/HRI by NAIs remained low, 0.5% (165/35045) and 0.6% (159/26010) for the 2018-2019 and 2019-2020 periods, respectively. The most common amino acid substitution was NA-H275Y (N1 numbering) conferring HRI by oseltamivir and peramivir in A(H1N1)pdm09 viruses. Combined phenotypic and PA sequence-based analysis showed that the global frequency of viruses showing reduced susceptibility to baloxavir or carrying substitutions associated with reduced susceptibility was low, 0.5% (72/15906) and 0.1% (18/15692) for the 2018-2019 and 2019-2020 periods, respectively. Most (n = 61) of these viruses had I38→T/F/M/S/L/V PA amino acid substitutions. In Japan, where baloxavir use was highest, the rate was 4.5% (41/919) in the 2018-2019 period and most of the viruses (n = 32) had PA-I38T. Zoonotic viruses isolated from humans (n = 32) in different countries did not contain substitutions in NA associated with NAI RI/HRI phenotypes. One A(H5N6) virus had a dual substitution PA-I38V + PA-E199G, which may reduce susceptibility to baloxavir. Therefore, NAIs and baloxavir remain appropriate choices for the treatment of influenza virus infections, but close monitoring of antiviral susceptibility is warranted.
Topics: Amino Acid Substitution; Antiviral Agents; Dibenzothiepins; Drug Resistance, Viral; Endonucleases; Enzyme Inhibitors; Humans; Influenza A Virus, H1N1 Subtype; Influenza B virus; Influenza, Human; Morpholines; Neuraminidase; Oseltamivir; Pyridones; Triazines
PubMed: 35292289
DOI: 10.1016/j.antiviral.2022.105281 -
Antiviral Research Apr 2024While clinical trials have illuminated both the virological and clinical efficacy of baloxavir for influenza and post-treatment viral resistance, these aspects warrant... (Observational Study)
Observational Study
While clinical trials have illuminated both the virological and clinical efficacy of baloxavir for influenza and post-treatment viral resistance, these aspects warrant further study in real-world settings. In response, we executed a prospective, observational study of the Japanese 2022-2023 influenza season. A cohort of 73 A(H3N2)-diagnosed outpatients-36 treated with baloxavir, 20 with oseltamivir, and 17 with other neuraminidase inhibitors (NAIs)-were analyzed. Viral samples were collected before and after administering an antiviral on days 1, 5, and 10, respectively. Cultured viruses were amplified using RT-PCR and sequenced to detect mutations. Fever and other symptoms were tracked via self-reporting diaries. In the baloxavir cohort, viral detection was 11.1% (4/36) and 0% (0/36) on day 5 and day 10, respectively. Two isolates from day 5 (5.6%, 2/36) manifested I38T/M-substitutions in the polymerase acidic protein (PA). For oseltamivir and other NAIs, viral detection rates were 60.0% (12/20) and 52.9% (9/17) on day 5, and 16.7% (3/18) and 6.3% (1/16) on day 10, respectively. No oseltamivir-resistant neuraminidase mutations were identified after treatment. Median fever durations for the baloxavir, oseltamivir, and other NAI cohorts were 27.0, 38.0, and 36.0 h, respectively, with no significant difference. Two patients harboring PA I38T/M-substitutions did not exhibit prolonged fever or other symptoms. These findings affirm baloxavir's virological and clinical effectiveness against A(H3N2) in the 2022-2023 season and suggest limited clinical influence of post-treatment resistance emergence.
Topics: Humans; Influenza, Human; Oseltamivir; Neuraminidase; Influenza A Virus, H3N2 Subtype; Outpatients; Seasons; Prospective Studies; Antiviral Agents; Pyridones; Enzyme Inhibitors; Guanidines; Fever; Dibenzothiepins; Morpholines; Triazines
PubMed: 38430970
DOI: 10.1016/j.antiviral.2024.105853 -
International Journal of Infectious... Mar 2023The effectiveness of oseltamivir versus peramivir in children infected with influenza remains unclear. This study aimed to evaluate their effectiveness in young children...
OBJECTIVES
The effectiveness of oseltamivir versus peramivir in children infected with influenza remains unclear. This study aimed to evaluate their effectiveness in young children (aged 0-5 years) infected with severe influenza A virus (IAV) or influenza B virus (IBV).
METHODS
We analyzed a cohort of 1662 young children with either IAV (N = 1095) or IBV (N = 567) who received oseltamivir or peramivir treatment from January 1, 2018 to March 31, 2022. Propensity score matching methods were applied to match children who were oseltamivir-treated versus peramivir-treated.
RESULTS
Children who were IAV-infected and IBV-infected shared similar features, such as influenza-associated symptoms and comorbidities at baseline. Among children infected with IAV with bacterial coinfection, the recovery rate was significantly greater in children treated with oseltamivir than in children treated with peramivir (15.6% vs 4.4%, P = 0.01). The median duration of hospitalization was also shorter in children treated with oseltamivir. Among children infected with IAV without bacterial coinfection, the recovery rate was greater in children treated with oseltamivir than in children treated with peramivir (21.1% vs 3.7%, P = 0.002). However, oseltamivir and peramivir offered similar recovery rates and duration of hospitalization (P >0.05 for both) among children infected with IBV.
CONCLUSION
Oseltamivir and peramivir exhibit similar effectiveness in young children with severe influenza B, whereas oseltamivir demonstrated improved recovery and shorter hospitalization in the treatment of severe influenza A in hospitalized children.
Topics: Child; Humans; Child, Preschool; Oseltamivir; Influenza, Human; Antiviral Agents; Child, Hospitalized; Coinfection; Influenza A virus; Influenza B virus; Treatment Outcome
PubMed: 36608788
DOI: 10.1016/j.ijid.2022.12.043 -
Pediatrics International : Official... Jan 2022Previous reports have not clarified the difference in clinical efficacy between baloxavir and oseltamivir against influenza. (Observational Study)
Observational Study
BACKGROUND
Previous reports have not clarified the difference in clinical efficacy between baloxavir and oseltamivir against influenza.
METHODS
A prospective observational study was performed during 2017-2018, 2018-2019, and 2019-2020 influenza seasons. The primary endpoint of this study was to compare the duration of fever between patients who received baloxavir and those who received oseltamivir.
RESULTS
A total of 235 influenza-infected patients (3-18 years of age), including 91 who received oseltamivir and 144 who received baloxavir, were enrolled. The proportions of influenza A(H3N2) virus, influenza A(H1N1)pdm09 virus, and influenza B virus-infected patients were 31.5%, 42.6%, and 26.0%, respectively. Patients who received oseltamivir were significantly younger than those who received baloxavir. Univariate analyses showed that the duration of fever was shorter with baloxavir than with oseltamivir against influenza virus overall, influenza A virus, influenza B virus, and influenza A(H1N1)pdm09 virus, but not for influenza A(H3N2) virus. In multivariate analyses, hazard ratios for influenza virus overall (0.53 [95% CI, 0.38-0.73]), influenza B virus (0.16 [95% CI, 0.07-0.41]), and influenza A(H1N1)pdm09 virus (0.55 [95% CI, 0.32-0.93]) were significantly lower in the patients who received baloxavir than those who received oseltamivir. However, the differences between influenza A virus and influenza A(H3N2) virus were not significant between the two groups.
CONCLUSION
For influenza virus overall, influenza B virus, and influenza A(H1N1)pdm09 virus, baloxavir treatment resulted in shorter duration of fever than oseltamivir treatment, but not for influenza A virus and influenza A(H3N2) virus.
Topics: Antiviral Agents; Dibenzothiepins; Humans; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza A virus; Influenza B virus; Influenza, Human; Morpholines; Oseltamivir; Pyridones; Seasons; Treatment Outcome; Triazines
PubMed: 35790049
DOI: 10.1111/ped.15169