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https://www.readbyqxmd.com/read/29214495/comparison-of-anti-influenza-virus-activity-and-pharmacokinetics-of-oseltamivir-free-base-and-oseltamivir-phosphate
#1
Jin Soo Shin, Keun Bon Ku, Yejin Jang, Yi-Seul Yoon, Daeho Shin, Oh Seung Kwon, Yun Young Go, Seong Soon Kim, Myoung Ae Bae, Meehyein Kim
Influenza viruses are major human respiratory pathogens that cause high morbidity and mortality worldwide. Currently, prophylactic vaccines and therapeutic antiviral agents are used to prevent and control influenza virus infection. Oseltamivir free base (OSV-FB), a modified generic antiviral drug of Tamiflu (oseltamivir phosphate, OSV-P), was launched in the Republic of Korea last year. Here, we examine the bioequivalence of these two compounds by assessing their antiviral efficacy in infected cells and in a mouse model...
December 2017: Journal of Microbiology / the Microbiological Society of Korea
https://www.readbyqxmd.com/read/29100887/a-pharmacologically-immunosuppressed-mouse-model-for-assessing-influenza-b-virus-pathogenicity-and-oseltamivir-treatment
#2
Bindumadhav M Marathe, Heba H Mostafa, Peter Vogel, Philippe Noriel Q Pascua, Jeremy C Jones, Charles J Russell, Richard J Webby, Elena A Govorkova
Immunocompromised patients are highly susceptible to influenza virus infections. Although neuraminidase inhibitor (NAI) therapy has proved effective in these patients, the treatment regimens require optimization, which can be partly addressed via animal models. Here, we describe a pharmacologically immunosuppressed mouse model for studying the pathogenesis of influenza B viruses and evaluating the efficacy of antiviral treatment. We modeled clinical regimens for dexamethasone and cyclophosphamide to immunosuppress BALB/c mice that were then inoculated with B/Phuket/3073/2013 (Yamagata lineage) or B/Brisbane/60/2008 (BR/08, Victoria lineage) virus...
October 31, 2017: Antiviral Research
https://www.readbyqxmd.com/read/29091888/oroxylin-a-suppresses-influenza-a-virus-replication-correlating-with-neuraminidase-inhibition-and-induction-of-ifns
#3
Jing Jin, Shuo Chen, Dechuan Wang, Yuanjin Chen, Yuxu Wang, Min Guo, Changlin Zhou, Jie Dou
Because it is highly contagious, the influenza A virus (IAV) has the potential to cause pandemics in humans. The emergence of drug-resistant strains requires the development of new chemical therapeutics. Oroxylin A (OA) is a flavonoid which has been shown to have antioxidant and antitumor effects. However, intensive studies in which OA fights against different influenza virus strains and the underlying antiviral mechanisms have not been reported. In our study, the antiviral activities in cells and in mice, the preliminary mechanisms of OA were investigated...
October 27, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29090056/oseltamivir-tamiflu-induced-bilateral-ciliochoroidal-effusion-and-angle-closure-glaucoma-what-type-of-idiosyncratic-reaction
#4
Shahin Yazdani, Hamed Esfandiari, Sare Safi, Alireza Fatemi
PURPOSE: To report a case of bilateral acute angle closure glaucoma after one dose of oseltamivir 75 mg. CASE REPORT: A 37-year-old man with a history of influenza developed high intraocular pressure and uniformly shallow anterior chamber in both eyes, 5 hours after the first dose of oseltamivir 75 mg. The condition was managed successfully with topical cycloplegic and systemic/topical antiglaucoma medications. CONCLUSION: Since a presumed idiosyncratic reaction developed right after the first dose of the medication, it challenges the common concept of adaptive immune system involvement in this type of reaction in medication-related ciliochoroidal effusion...
October 2017: Journal of Ophthalmic & Vision Research
https://www.readbyqxmd.com/read/29066417/combined-aerosolized-toll-like-receptor-ligands-are-an-effective-therapeutic-agent-against-influenza-pneumonia-when-co-administered-with-oseltamivir
#5
Miguel M Leiva-Juarez, Carson T Kirkpatrick, Brian E Gilbert, Brenton Scott, Michael J Tuvim, Burton F Dickey, Scott E Evans, Diane Markesich
Influenza pneumonia remains a common and debilitating viral infection despite vaccination programs and antiviral agents developed for prophylaxis and treatment. The neuraminidase inhibitor oseltamivir is frequently prescribed for established influenza A virus infections, but the emergence of neuraminidase inhibitor resistant viruses, a brief therapeutic window and competing diagnoses complicate its use. PUL-042 is a clinical stage, aerosol drug comprised of synthetic ligands for Toll-like receptor (TLR) 2/6 and TLR 9...
October 21, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28958678/oseltamivir-amantadine-and-ribavirin-combination-antiviral-therapy-versus-oseltamivir-monotherapy-for-the-treatment-of-influenza-a-multicentre-double-blind-randomised-phase-2-trial
#6
John H Beigel, Yajing Bao, Joy Beeler, Weerawat Manosuthi, Alex Slandzicki, Sadia M Dar, John Panuto, Richard L Beasley, Santiago Perez-Patrigeon, Gompol Suwanpimolkul, Marcelo H Losso, Natalie McClure, Dawn R Bozzolo, Christopher Myers, H Preston Holley, Justin Hoopes, H Clifford Lane, Michael D Hughes, Richard T Davey
BACKGROUND: Influenza continues to have a substantial socioeconomic and health impact despite a long established vaccination programme and approved antivirals. Preclinical data suggest that combining antivirals might be more effective than administering oseltamivir alone in the treatment of influenza. METHODS: We did a randomised, double-blind, multicentre phase 2 trial of a combination of oseltamivir, amantadine, and ribavirin versus oseltamivir monotherapy with matching placebo for the treatment of influenza in 50 sites, consisting of academic medical centre clinics, emergency rooms, and private physician offices in the USA, Thailand, Mexico, Argentina, and Australia...
September 22, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28948652/pharmacokinetic-changes-of-antibiotic-antiviral-antituberculosis-and-antifungal-agents-during-extracorporeal-membrane-oxygenation-in-critically-ill-adult-patients
#7
REVIEW
J Hahn, J H Choi, M J Chang
WHAT IS KNOWN AND OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) is a life-saving system used for critically ill patients with cardiac and/or respiratory failure. The pharmacokinetics (PK) of drugs can change in patients undergoing ECMO, which can result in therapeutic failure or drug toxicity requiring further management of drug complications. In this review, we discussed changes in the PK of antibiotic, antiviral, antituberculosis and antifungal agents administered to adult patients on ECMO...
September 25, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28936484/cetylpyridinium-chloride-cpc-exhibits-potent-rapid-activity-against-influenza-viruses-in-vitro-and-in-vivo
#8
Daniel L Popkin, Sarah Zilka, Matthew Dimaano, Hisashi Fujioka, Cristina Rackley, Robert Salata, Alexis Griffith, Pranab K Mukherjee, Mahmoud A Ghannoum, Frank Esper
BACKGROUND: There is a continued need for strategies to prevent influenza. While cetylpyridinium chloride (CPC), a broad-spectrum antimicrobial agent, has an extensive antimicrobial spectrum, its ability to affect respiratory viruses has not been studied in detail. OBJECTIVES: Here, we evaluate the ability of CPC to disrupt influenza viruses in vitro and in vivo. METHODS: The virucidal activity of CPC was evaluated against susceptible and oseltamivir-resistant strains of influenza viruses...
2017: Pathogens & Immunity
https://www.readbyqxmd.com/read/28931216/emergence-of-oseltamivir-resistant-h7n9-influenza-viruses-in-immunosuppressed-cynomolgus-macaques
#9
Maki Kiso, Kiyoko Iwatsuki-Horimoto, Seiya Yamayoshi, Ryuta Uraki, Mutsumi Ito, Noriko Nakajima, Shinya Yamada, Masaki Imai, Eiryo Kawakami, Yuriko Tomita, Satoshi Fukuyama, Yasushi Itoh, Kazumasa Ogasawara, Tiago J S Lopes, Tokiko Watanabe, Louise H Moncla, Hideki Hasegawa, Thomas C Friedrich, Gabriele Neumann, Yoshihiro Kawaoka
Antiviral compounds (eg, the neuraminidase inhibitor oseltamivir) are invaluable for the treatment of individuals infected with influenza A viruses of the H7N9 subtype (A[H7N9]), which have infected and killed hundreds of persons. However, oseltamivir treatment often leads to the emergence of resistant viruses in immunocompromised individuals. To better understand the emergence and properties of oseltamivir-resistant A(H7N9) viruses in immunosuppressed individuals, we infected immunosuppressed cynomolgus macaques with an A(H7N9) virus and treated them with oseltamivir...
September 1, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28852683/successful-treatment-of-influenza-associated-acute-necrotizing-encephalitis-in-an-adult-using-high-dose-oseltamivir-and-methylprednisolone-case-report-and-literature-review
#10
REVIEW
Ahmed Alsolami, Kevin Shiley
A case of influenza-associated acute necrotizing encephalitis (ANE) is described in an otherwise healthy adult. The patient was treated successfully with a combination of high-dose methylprednisolone and high-dose oseltamivir. The patient relapsed after discontinuing 150 mg twice daily oseltamivir but quickly improved and eventually recovered after reinitiation of high-dose oseltamivir for an additional 2 weeks. The clinical presentation, pathogenesis, and treatment of influenza-associated ANE is reviewed. The use of high-dose oseltamivir in combination with methylprednisolone may offer additional therapeutic benefit for this rare and poorly understood complication of influenza infection...
2017: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28827718/broadly-protective-murine-monoclonal-antibodies-against-influenza-b-virus-target-highly-conserved-neuraminidase-epitopes
#11
Teddy John Wohlbold, Kira A Podolsky, Veronika Chromikova, Ericka Kirkpatrick, Veronica Falconieri, Philip Meade, Fatima Amanat, Jessica Tan, Benjamin R tenOever, Gene S Tan, Sriram Subramaniam, Peter Palese, Florian Krammer
A substantial proportion of influenza-related childhood deaths are due to infection with influenza B viruses, which co-circulate in the human population as two antigenically distinct lineages defined by the immunodominant receptor binding protein, haemagglutinin. While broadly cross-reactive, protective monoclonal antibodies against the haemagglutinin of influenza B viruses have been described, none targeting the neuraminidase, the second most abundant viral glycoprotein, have been reported. Here, we analyse a panel of five murine anti-neuraminidase monoclonal antibodies that demonstrate broad binding, neuraminidase inhibition, in vitro antibody-dependent cell-mediated cytotoxicity and in vivo protection against influenza B viruses belonging to both haemagglutinin lineages and spanning over 70 years of antigenic drift...
October 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28807912/phase-2-randomized-trial-of-the-safety-and-efficacy-of-mhaa4549a-a-broadly-neutralizing-monoclonal-antibody-in-a-human-influenza-a-virus-challenge-model
#12
Jacqueline M McBride, Jeremy J Lim, Tracy Burgess, Rong Deng, Michael A Derby, Mauricio Maia, Priscilla Horn, Omer Siddiqui, Daniel Sheinson, Haiyin Chen-Harris, Elizabeth M Newton, Dimitri Fillos, Denise Nazzal, Carrie M Rosenberger, Maikke B Ohlson, Rob Lambkin-Williams, Hosnieh Fathi, Jeffrey M Harris, Jorge A Tavel
MHAA4549A, a human monoclonal antibody targeting the hemagglutinin stalk region of influenza A virus (IAV), is being developed as a therapeutic for patients hospitalized with severe IAV infection. The safety and efficacy of MHAA4549A were assessed in a randomized, double-blind, placebo-controlled, dose-ranging study in a human IAV challenge model. One hundred healthy volunteers were inoculated with A/Wisconsin/67/2005 (H3N2) IAV and, 24 to 36 h later, administered a single intravenous dose of either placebo, MHAA4549A (400, 1,200, or 3,600 mg), or a standard oral dose of oseltamivir...
November 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28792077/the-combination-of-oseltamivir-with-azithromycin-does-not-show-additional-benefits-over-oseltamivir-monotherapy-in-mice-infected-with-influenza-a-h1n1-pdm2009-virus
#13
Clément Fage, Andrés Pizzorno, Chantal Rhéaume, Yacine Abed, Guy Boivin
The combination of azithromycin, an immunomodulator, with oseltamivir was compared to oseltamivir monotherapy in a lethal BALB/c model of influenza A(H1N1)pdm09 infection. Groups of 14-16 mice received oral oseltamivir (10 mg/kg once daily for 5 days, starting at day 2 post-inoculation) alone or combined to azithromycin (a single 100 mg/kg dose, injected intraperitoneally at day 3 post-inoculation). Based on survival rates, lung viral titers, and pro-inflammatory cytokine levels, the combination therapy did not provide obvious additional clinical/virological benefits over oseltamivir monotherapy...
December 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28738449/pbpk-modeling-of-the-effect-of-reduced-kidney-function-on-the-pharmacokinetics-of-drugs-excreted-renally-by-organic-anion-transporters
#14
C-H Hsueh, V Hsu, P Zhao, L Zhang, K M Giacomini, S-M Huang
Altered pharmacokinetics (PK) in subjects with chronic kidney disease (CKD) may lead to dosing adjustment of certain drugs in subjects with CKD. It can be valuable to quantitatively predict PK in CKD for the management of drug dosing in these subjects. We developed physiologically based pharmacokinetic (PBPK) models of seven renally eliminated drugs: adefovir, avibactam, entecavir, famotidine, ganciclovir, oseltamivir carboxylate, and sitagliptin. These drugs are all substrates of renal organic anion transporters (OATs)...
July 24, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28737128/bioequivalence-of-two-oseltamivir-formulations-in-healthy-chinese-volunteers%C3%A2
#15
RANDOMIZED CONTROLLED TRIAL
Yun-Lei Yun, Shou-Hong Gao, Yan Wen, Zhi-Peng Wang, Hai-Jun Miao, Wan-Sheng Chen
BACKGROUND: The aim of this study was to compare the bioavailability of a new generic formulation of oseltamivir 75-mg capsule (test) and a branded formulation Tamiflu<sup>®</sup> (reference) to meet regulatory criteria for marketing the test product in healthy Chinese male volunteers. METHODS: This single-dose, randomized-sequence, open-label, two-period crossover study was conducted in fasted healthy Chinese male volunteers, who first received a single oral dose of the test or reference formulation with a 7-day washout period, and then the alternative formulation...
September 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28698321/factors-associated-with-non-persistence-to-oral-and-inhaled-antiviral-therapies-for-seasonal-influenza-a-secondary-analysis-of-a-double-blind-multicentre-randomised-clinical-trial
#16
Remi Flicoteaux, Camelia Protopopescu, Annick Tibi, Thierry Blanchon, Sylvie Van Der Werf, Xavier Duval, Anne Mosnier, Cécile Charlois-Ou, Bruno Lina, Catherine Leport, Sylvie Chevret
OBJECTIVES: We aimed to evaluate and compare non-adherence to oral and inhaled antiviral therapies prescribed of a randomised clinical trial in outpatients with influenza A infection. DESIGN: A parallel, three-arm, double-blinded trial randomly allocated antiviral therapies twice daily for 5 days: (1) oral oseltamivir plus inhaled zanamivir (arm OZ); (2) oseltamivir plus inhaled placebo (arm Opz); or (3) oral placebo plus inhaled zanamivir (arm poZ). Analysis of non-adherence was a secondary objective of the trial...
July 10, 2017: BMJ Open
https://www.readbyqxmd.com/read/28688289/antiviral-activity-of-a-synthesized-shikonin-ester-against-influenza-a-h1n1-virus-and-insights-into-its-mechanism
#17
Yahan Zhang, Hongwei Han, Hanyue Qiu, Hongyan Lin, Lugang Yu, Wanzhan Zhu, Jinliang Qi, Rongwu Yang, Yanjun Pang, Xiaoming Wang, Guihua Lu, Yonghua Yang
This study aimed to examine the antiviral effects of shikonin ester ((R)-1-(5, 8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl3-(1H- indol-3-yl) propanoate (PMM-034) against influenza A (H1N1) virus. We investigated PMM-034 anti-H1N1 activity and its effect on caspase 3 gene expression during cellular apoptosis after influenza virus infection in vitro. Neuraminidase (NA) inhibition was assessed in comparison with oseltamivir in the influenza virus standard strains A/PR/8/34 to understand the viral mechanism...
September 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28674259/pinanamine-is-a-promising-lead-compound-against-influenza-a-virus-evidence-from-in-vitro-and-in-vivo-efficacy-compared-to-amantadine
#18
Runfeng Li, Chunguang Yang, Qiuling Du, Xin Zhao, Haiming Jiang, Wenhui Hu, Zifeng Yang
Influenza A viruses with the presence of mutations in M2 still circulate and threaten to avian species and human in China. A novel M2 inhibitor pinanamine was previously identified as an antiviral agent by an in vitro assay. In this study, we monitored the activity of pinanamine against influenza A/FM1/47 (H1N1) virus infection in cell culture and mice. Pinanamine showed more potent antiviral effect than ribavirin, and was as effective as oseltamivir carboxylate and amantadine in Madin-Darby canine kidney (MDCK) cells...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28639229/pharmacokinetics-of-mhaa4549a-an-anti-influenza-a-monoclonal-antibody-in-healthy-subjects-challenged-with-influenza%C3%A2-a-virus-in-a-phase-iia-randomized-trial
#19
Rong Deng, Ai Ping Lee, Mauricio Maia, Jeremy J Lim, Tracy Burgess, Priscilla Horn, Michael A Derby, Elizabeth Newton, Jorge A Tavel, William D Hanley
BACKGROUND AND OBJECTIVES: MHAA4549A, a human anti-influenza immunoglobulin (Ig) G1 monoclonal antibody, is being developed to treat patients hospitalized for influenza A infection. This study examined the pharmacokinetics (PKs) of MHAA4549A in a phase IIa, randomized, double-blind, dose-ranging trial in healthy volunteers challenged with influenza A virus. METHODS: Serum PK data were collected from 60 subjects in three single-dose groups (400, 1200, or 3600 mg) who received MHAA4549A intravenously 24-36 h after inoculation with the influenza A virus...
June 21, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28633457/the-hemagglutinin-a-stem-antibody-medi8852-prevents-and-controls-disease-and-limits-transmission-of-pandemic-influenza-viruses
#20
Catharine I Paules, Seema Lakdawala, Josephine M McAuliffe, Myeisha Paskel, Leatrice Vogel, Nicole L Kallewaard, Qing Zhu, Kanta Subbarao
Background: MEDI8852 is a novel monoclonal antibody (mAb) that neutralizes both group I and group II influenza A viruses (IAVs) in vitro. We evaluated whether MEDI8852 was effective for prophylaxis and therapy against representative group I (H5N1) and group II (H7N9) pandemic IAVs in mice and ferrets and could be used to block transmission of influenza H1N1pdm09 in ferrets, compared to an irrelevant control mAb R347 and oseltamivir. Methods: MEDI8852 was administered to mice and ferrets by intraperitoneal injection at varying doses, 24 hours prior to intranasal infection with H5N1 and H7N9 viruses for prophylaxis, and 24, 48, and 72 hours post-infection for treatment...
August 1, 2017: Journal of Infectious Diseases
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