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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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/safety-and-efficacy-of-mhaa4549a-a-broadly-neutralizing-monoclonal-antibody-in-a-human-influenza-a-challenge-model-a-phase-2-randomized-trial
#7
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
BACKGROUND: 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. Safety and efficacy of MHAA4549A were assessed in a randomized, double-blind, placebo-controlled, dose-ranging study in a human IAV-challenge model. METHODS: One hundred healthy volunteers were inoculated with A/Wisconsin/67/2005 (H3N2) IAV and, 24-36 hours later, administered a single intravenous dose of either placebo, MHAA4549A (400, 1200, or 3600 mg) or a standard oral dose of oseltamivir...
August 14, 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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
https://www.readbyqxmd.com/read/28540991/comparison-of-efficacy-of-intravenous-peramivir-and-oral-oseltamivir-for-the-treatment-of-influenza-systematic-review-and-meta-analysis
#16
REVIEW
Jonghoo Lee, Ju Hee Park, Hyeyoung Jwa, Yee Hyung Kim
PURPOSE: Peramivir is the first intravenously administered neuramidase inhibitor for immediate delivery of an effective single-dose treatment in patients with influenza. However, limited data are available on intravenous (IV) peramivir treatment compared to oral oseltamivir for these patients. MATERIALS AND METHODS: With a systematic review and meta-analysis, we compared the efficacy of IV peramivir with oral oseltamivir for treatment of patients with seasonal influenza...
July 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/28539708/assessment-of-mexican-arnica-heterotheca-inuloides-cass-and-rosemary-rosmarinus-officinalis-extracts-on-dopamine-and-selected-biomarkers-of-oxidative-stress-in-stomach-and-brain-of-salmonella-typhimurium-infected-rats
#17
David Calderón Guzmàn, Maribel Ortiz Herrera, Norma Osnaya Brizuela, Gerardo Barragàn Mejía, Ernestina Hernàndez García, Hugo Juàrez Olguín, Armando Valenzuela Peraza, Norma Labra Ruíz, Daniel Santamaría Del Angel
BACKGROUND: The effects of some natural products on dopamine (DA) and 5-hydroxyindole acetic acid (5-HIAA) in brain of infected models are still unclear. OBJECTIVE: The purpose of this study was to measure the effect of Mexican arnica/rosemary (MAR) water extract and oseltamivir on both biogenic amines and some oxidative biomarkers in the brain and stomach of young rats under infection condition. METHODS: Female Wistar rats (weight 80 g) in the presence of MAR or absence (no-MAR) were treated as follows: group 1, buffer solution (controls); oseltamivir (100 mg/kg), group 2; culture of Salmonella typhimurium (S...
April 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28496342/sialylation-facilitates-self-assembly-of-3d-multicellular-prostaspheres-by-using-cyclo-rgdfk-tpp-peptide
#18
Sabah Haq, Vanessa Samuel, Fiona Haxho, Roman Akasov, Maria Leko, Sergey V Burov, Elena Markvicheva, Myron R Szewczuk
BACKGROUND: Prostaspheres-based three dimensional (3D) culture models have provided insight into prostate cancer (PCa) biology, highlighting the importance of cell-cell interactions and the extracellular matrix (EMC) in the tumor microenvironment. Although these 3D classical spheroid platforms provide a significant advance over 2D models mimicking in vivo tumors, the limitations involve no control of assembly and structure with only limited spatial or glandular organization. Here, matrix-free prostaspheres from human metastatic prostate carcinoma PC3 and DU145 cell lines and their respective gemcitabine resistant (GemR) variants were generated by using cyclic Arg-Gly-Asp-D-Phe-Lys peptide modified with 4-carboxybutyl-triphenylphosphonium bromide (cyclo-RGDfK(TPP))...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28474821/application-of-physiologically-based-pharmacokinetic-modeling-to-predict-drug-disposition-in-pregnant-populations
#19
Vamshi Krishna Jogiraju, Suvarchala Avvari, Rakesh Gollen, David R Taft
Pregnancy is associated with numerous physiological changes that influence absorption, distribution, metabolism and excretion. Moreover, the magnitude of these effects changes as pregnancy matures. For most medications, there is limited information available about changes in drug disposition that can occur in pregnant patients, yet most women are prescribed one or more medications during pregnancy. In this investigation, PBPK modeling was used to assess the impact of pregnancy on the pharmacokinetic profiles of three medications (metformin, tacrolimus, oseltamivir) using the Simcyp® simulator...
May 5, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28437488/the-novel-carboxylesterase-1-variant-c-662a-g-may-decrease-the-bioactivation-of-oseltamivir-in-humans
#20
Jaeseong Oh, SeungHwan Lee, Howard Lee, Joo-Youn Cho, Seo Hyun Yoon, In-Jin Jang, Kyung-Sang Yu, Kyoung Soo Lim
BACKGROUND: Human carboxylesterase 1 (CES1) is a serine esterase that hydrolyses various exogenous and endogenous compounds including oseltamivir, a prodrug used to treat influenza. A novel CES1 c.662A>G single nucleotide polymorphism (SNP) was predicted to decrease CES1 enzymatic activity in an in silico analysis. This study evaluated the effect of the c.662A>G SNP on the pharmacokinetics (PK) of oseltamivir in humans. METHODS: A single oral dose of oseltamivir at 75 mg was administered to 20 healthy subjects, 8 heterozygous c...
2017: PloS One
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