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Platelets Nov 2020Desialylation of platelets results in platelet clearance by the Ashwell-Morrell Receptors (AMR) found on hepatocytes. Studies suggest that oseltamivir phosphate inhibits... (Review)
Review
Desialylation of platelets results in platelet clearance by the Ashwell-Morrell Receptors (AMR) found on hepatocytes. Studies suggest that oseltamivir phosphate inhibits human sialidases, enzymes responsible for desialylation, extending the lifespan of circulating platelets. We thus evaluated, the effects of oseltamivir on platelet count (PC) following treatment. Of the 385 patients evaluated for influenza, 283 (73.5%) were influenza-infected. Of the 283 infected patients, 241 (85.2%) received oseltamivir (I + O+) while 42 patients did not (I + O-). One hundred two non-infected patients received oseltamivir (I-O+). The two groups receiving oseltamivir (I + O+, I-O+), demonstrated a statistically greater increase in the PC (57.53 ± 93.81, = .013 and 50.79 ± 70.59, = .023, respectively) relative to the group that did not (18.45 ± 89.33 × 10/L). The observed increase in PC was statistically similar ( = .61) in both groups receiving oseltamivir (I + O+, I-O+), suggesting that this effect is independent of influenza. Comparing clinical characteristics between responders and non-responders to oseltamivir treatment showed that only duration of oseltamivir treatment (AOR = 1.30, 95% CI 1.05-1.61, = .015) was associated with a positive PC response. Our findings suggest a correlation between oseltamivir treatment and an increase in PCs. Future studies assessing the possible uses of oseltamivir in medical conditions characterized by diminished or defective thrombopoiesis are warranted.
Topics: Aged; Humans; Middle Aged; Oseltamivir; Platelet Count; Retrospective Studies
PubMed: 31931672
DOI: 10.1080/09537104.2020.1714576 -
Biochimica Et Biophysica Acta.... Mar 2024Oseltamivir belongs to the neuraminidase inhibitors, developed against the influenza virus, and registered under the trademark Tamiflu. Despite its long-term...
Oseltamivir belongs to the neuraminidase inhibitors, developed against the influenza virus, and registered under the trademark Tamiflu. Despite its long-term acquaintance, there is limited information in the literature about its physicochemical and structural properties in a lipid-water system. We present an experimentally determined partition coefficient with structural information on the interaction of oseltamivir with the model membrane, its possible location, and its effect on the membrane thermodynamics. The hydrophobic part of the lipid bilayer is affected to a moderate extent, which was proved by slight changes in thermal and structural properties. Hereby, interaction of oseltamivir with the phospholipid bilayer induces concentration dependent decrease of lateral pressure in the bilayer acyl chain region. Oseltamivir charges the bilayer surface positively, which results in the zeta potential increase and changes in anisotropic properties studied by the polarised light microscopy. At the highest oseltamivir concentrations studied, the multilamellar structure is extensively disturbed, likely due to electrostatic repulsion between the adjacent bilayers.
Topics: Oseltamivir; Antiviral Agents; Lipid Bilayers; Phospholipids; Phosphates
PubMed: 38211646
DOI: 10.1016/j.bbamem.2024.184273 -
BMC Pharmacology & Toxicology Feb 2023The study was aimed at evaluating the bioequivalence and safety of oseltamivir phosphate for suspension, provided by Shenzhen Beimei Pharmaceutical Co. Ltd. and... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
The study was aimed at evaluating the bioequivalence and safety of oseltamivir phosphate for suspension, provided by Shenzhen Beimei Pharmaceutical Co. Ltd. and manufactured by Hetero Labs Limited, and the reference product TAMIFLU® in healthy Chinese subjects.
METHODS
A single-dose, randomized, two-phase, self-crossed model was adopted. Among 80 healthy subjects, 40 subjects in the fasting group and 40 subjects in the fed group. Subjects in the fasting group were randomized into two sequences according to the proportion of 1:1, each given 75 mg/12.5 mL of Oseltamivir Phosphate for Suspension or TAMIFLU®, and cross-administered after 7 days. Postprandial group is the same as fasting group.
RESULTS
The T of TAMIFLU® and Oseltamivir Phosphate for Suspension in the fasting group were 1.50 h and 1.25 h, which in the fed group were both 1.25 h. Geometrically adjusted mean ratios of the PK parameters of Oseltamivir Phosphate for Suspension along with TAMIFLU® under fasting and postprandial conditions were in the range of 80.00-125.00% at the 90% confidence interval (CI). The 90% CI of C, AUC, AUC for fasting group and postprandial group were (92.39,106.50), (94.26,100.67), (94.32,100.89) and (93.61,105.83),(95.64,100.19),(96.06,102.66). Among the subjects on medication, a total of 18 subjects reported 27 adverse events, all of which were treatment-emergent adverse events (TEAEs), six of these TEAEs were rated as grade 2 in severity and the rest were as grade 1. The number of TEAEs in the test product and the reference product were 14,13 respectively.
CONCLUSION
Two Oseltamivir phosphate for suspensions are safe and bioequivalent.
Topics: Humans; Oseltamivir; Therapeutic Equivalency; Suspensions; Cross-Over Studies; Area Under Curve; Fasting; Healthy Volunteers; Phosphates; Tablets
PubMed: 36810140
DOI: 10.1186/s40360-023-00646-1 -
American Journal of Health-system... Feb 2000
Topics: Amines; Antiviral Agents; Contraindications; Humans; Influenza, Human; Oseltamivir
PubMed: 10674782
DOI: 10.1093/ajhp/57.3.282 -
Pediatric Nursing 2014Influenza is a highly contagious virus that causes an average of 20,000 hospitalizations a year in children under five years of age. As of March 30, 2013, the 2012-2013... (Review)
Review
Influenza is a highly contagious virus that causes an average of 20,000 hospitalizations a year in children under five years of age. As of March 30, 2013, the 2012-2013 flu season had seen 111 pediatric deaths, with 21 deaths in the 0- to 23-month-old range. Rates of influenza-associated hospitalization are substantially higher among infants and young children than among older children, and those under six months old are at the highest risk. Research shows that influenza vaccine is not as effective in children two years of age relative to adults, and the vaccine is not approved in infants younger than six months. Thus, preventing influenza and proper treatment are important for keeping this high-risk group safe from complications. With infants being highest at risk for complications and the extrapolation of efficacy and safety from the older population, the U.S. Food and Drug Administration (FDA) recently approved the use of the antiviral oseltamivir phosphate (Tamiflu) for treatment of uncomplicated influenza in patients two weeks and older. This young population is susceptible to the benefits as well as the risks of the drug. Health care providers must be aware of dosing, adverse reactions, and monitoring parameters to better treat and educate their patients.
Topics: Antiviral Agents; Child, Preschool; Contraindications; Humans; Infant; Infant, Newborn; Influenza Vaccines; Influenza, Human; Oseltamivir; United States
PubMed: 24757915
DOI: No ID Found -
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 -
Microvascular Research Jan 2022The target of the current investigation was the delivery of oseltamivir phosphate (OSE) into the lung adenocarcinoma tissues by means of designing nanosized, non-toxic...
Oseltamivir phosphate loaded pegylated-Eudragit nanoparticles for lung cancer therapy: Characterization, prolonged release, cytotoxicity profile, apoptosis pathways and in vivo anti-angiogenic effect by using CAM assay.
The target of the current investigation was the delivery of oseltamivir phosphate (OSE) into the lung adenocarcinoma tissues by means of designing nanosized, non-toxic and biocompatible pegylated Eudragit based NPs and investigating their anticancer and antiangiogenic activity. The rationale for this strategy is to provide a novel perspective to cancer treatment with OSE loaded pegylated ERS NPs under favor of smaller particle size, biocompatible feature, cationic characteristic, examining their selective effectiveness on lung cell lines (A549 lung cancer cell line and CCD-19Lu normal cell line) and examining antiangiogenic activity by in vivo CAM analysis. For this purpose, OSE encapsulated pegylated ERS based NPs were developed and investigated for zeta potential, particle size, encapsulation efficiency, morphology, DSC, FT-IR, H NMR analyses. In vitro release, cytotoxicity, determination apoptotic pathways and in vivo CAM assay were carried out. Considering characterizations, NPs showed smaller particle size, cationic zeta potential, relatively higher EE%, nearly spherical shape, amorphous matrix formation and prolonged release pattern (Peppas-Sahlin and Weibull model with Fickian and non-Fickian release mechanisms). Flow cytometry was used to assess the apoptotic pathways using the Annexin V-FITC/PI staining assay, FITC Active Caspase-3 staining assay, and mitochondrial membrane potential detection tests. Activations on caspase-3 pathways made us think that OSE loaded pegylated ERS NPs triggered to apoptosis using intrinsic pathway. As regards to the in vivo studies, OSE loaded pegylated ERS based NPs demonstrated strong and moderate antiangiogenic activity for ERS-OSE 2 and ERS-OSE 3, respectively. With its cationic character, smaller particle size, relative superior EE%, homogenous amorphous polymeric matrix constitution indicated using solid state tests, prolonged release manner, highly selective to the human lung adenocarcinoma cell lines, could trigger apoptosis intrinsically and effectively, possess good in vivo antiangiogenic activity, ERS-OSE 2 formulation is chosen as a promising candidate and a potent drug delivery system to treat lung cancer.
Topics: A549 Cells; Acrylic Resins; Angiogenesis Inhibitors; Animals; Apoptosis; Chick Embryo; Chorioallantoic Membrane; Delayed-Action Preparations; Drug Carriers; Drug Compounding; Drug Liberation; Humans; Lung Neoplasms; Nanoparticles; Nanotechnology; Neovascularization, Pathologic; Neovascularization, Physiologic; Oseltamivir; Polyethylene Glycols
PubMed: 34520775
DOI: 10.1016/j.mvr.2021.104251 -
Different synthetic strategies of oseltamivir phosphate: a potent influenza neuraminidase inhibitor.Current Medicinal Chemistry 2008Oseltamivir phosphate (Tamiflu) is the only orally active anti-influenza drug that potently inhibit neuraminidase. The recent emergence of avian flu, especially the H5N1... (Review)
Review
Oseltamivir phosphate (Tamiflu) is the only orally active anti-influenza drug that potently inhibit neuraminidase. The recent emergence of avian flu, especially the H5N1 type, makes the situation of Tamiflu supply and demand increasingly serious. Further optimization of the current commercial approach and exploration of new synthetic routes are urgent. Here, different synthetic strategies of oseltamivir phosphate are reviewed, including discovery and improved synthetic route from (-)-quinic acid or (-)-shikimic acid, new asymmetric synthesis via catalytic desymmetrization of a meso-aziridine (CDMA), Diels-Alder Reaction and from other available materials.
Topics: Antiviral Agents; Enzyme Inhibitors; Humans; Influenza A Virus, H5N1 Subtype; Influenza, Human; Molecular Conformation; Neuraminidase; Oseltamivir; Stereoisomerism; Structure-Activity Relationship
PubMed: 19075659
DOI: 10.2174/092986708786848497 -
Oseltamivir phosphate-Lifting the restriction on its use to treat teenagers with influenza in Japan.Pharmacoepidemiology and Drug Safety Apr 2019In 2007, Ministry of Health, Labour and Welfare (MHLW) warned to refrain from prescribing oseltamivir for teenagers when two Japanese teenagers with influenza fell from...
PURPOSE
In 2007, Ministry of Health, Labour and Welfare (MHLW) warned to refrain from prescribing oseltamivir for teenagers when two Japanese teenagers with influenza fell from a high-rise building after taking oseltamivir. Revisions of the warning texts of anti-influenza drugs were discussed by the Subcommittee of Pharmaceutical Affairs and Food Sanitation Council, MHLW, based on the studies and trends of anti-influenza medication over the last 10 years.
METHOD
The research group led by Dr Nobuhiko Okabe conducted nationwide survey since the 2007/2008 influenza season. The results of Japanese and foreign epidemiological and non-clinical studies of abnormal behaviors in influenza patients since 2009 were reviewed.
RESULT
Severe abnormal behaviors have been reported in influenza patients taking all types of anti-influenza drugs, as well as in untreated patients. There are some risks to patients whether treated with any anti-influenza drug, or non-treated though it is still not possible to rule out a potential causal relationship between abnormal behaviors and anti-influenza drugs. 70% of abnormal behaviors occurred within two days after the onset of fever. No difference was found between anti-influenza drugs treated and non-treated patients. In patients receiving oseltamivir and other anti-influenza drugs, the frequency of abnormal behaviors is not clearly different between teenagers and patients under 10 years old.
CONCLUSION
The specific "boxed warning" and the restriction only for oseltamivir that should not be used for teenagers was lifted. Therefore, the labeling of all anti-influenza drugs carry a consistent warning about the potential for abnormal behaviors in Japan.
Topics: Accidental Falls; Adolescent; Age Factors; Antiviral Agents; Behavioral Symptoms; Child; Child, Preschool; Drug Labeling; Female; Humans; Influenza, Human; Japan; Male; Oseltamivir; Severity of Illness Index; Young Adult
PubMed: 30834626
DOI: 10.1002/pds.4721 -
Journal of Cardiovascular Pharmacology May 2021Desialylation, governed by sialidases or neuraminidases, is strongly implicated in a wide range of human disorders, and accumulative data show that inhibition of...
Desialylation, governed by sialidases or neuraminidases, is strongly implicated in a wide range of human disorders, and accumulative data show that inhibition of neuraminidases, such as neuraminidases 1 sialidase, may be useful for managing atherosclerosis. Several studies have reported promising effects of oseltamivir phosphate, a widely used anti-influenza sialidase inhibitor, on human cancer cells, inflammation, and insulin resistance. In this study, we evaluated the effects of oseltamivir phosphate on atherosclerosis and thrombosis and potential liver toxicity in LDLR-/- mice fed with high-fat diet. Our results showed that oseltamivir phosphate significantly decreased plasma levels of LDL cholesterol and elastin fragmentation in aorta. However, no effect was observed on both atherosclerotic plaque size in aortic roots and chemically induced thrombosis in carotid arteries. Importantly, oseltamivir phosphate administration had adverse effects on the liver of mice and significantly increased messenger RNA expression levels of F4/80, interleukin-1β, transforming growth factor-β1, matrix metalloproteinase-12, and collagen. Taken together, our findings suggest that oseltamivir phosphate has limited benefits on atherosclerosis and carotid thrombosis and may lead to adverse side effects on the liver with increased inflammation and fibrosis.
Topics: Animals; Antiviral Agents; Aorta; Aortic Diseases; Atherosclerosis; Carotid Artery Thrombosis; Chemical and Drug Induced Liver Injury; Diet, High-Fat; Disease Models, Animal; Female; Liver; Liver Cirrhosis; Mice, Knockout; Oseltamivir; Plaque, Atherosclerotic; Receptors, LDL; Risk Assessment; Mice
PubMed: 33760798
DOI: 10.1097/FJC.0000000000001002