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Analytical and Bioanalytical Chemistry May 2016A simple, precise, and rapid method to simultaneously determine the levels of oseltamivir (OS) and oseltamivir carboxylate (OSC) in human plasma was developed....
A simple, precise, and rapid method to simultaneously determine the levels of oseltamivir (OS) and oseltamivir carboxylate (OSC) in human plasma was developed. Additionally, the stability of both substances in plasma was investigated under different conditions. The method involved protein precipitation (0.01 % HCl in acetonitrile), and then the supernatant was injected into the high-performance liquid chromatography (HPLC)-MS/MS. The chromatographic separation was achieved on a YMC-Triart C18 (100 × 2.0 mm, 5 μm) column using acetonitrile/water (30:70, v/v) containing 0.1 % formic acid as the mobile phase. Sample volume was 5 μl. The linearity of the method was established in the concentration range of 0.5-100 ng/mL for OS and 1.0-1000 ng/mL for OSC. The intra-day precision and accuracy for oseltamivir were 1.5-8.9 and 94.4-101.0 %, respectively. For oseltamivir carboxylate, the intra-day precision and accuracy were 3.2-12.7 and 92.8-108.8 %, respectively, whereas the inter-day precision and accuracy were 5.5-11.5 and 94.6-104.0 % for oseltamivir and 4.7-11.5 and 99.9-103.9 % for oseltamivir carboxylate, respectively. The application of this method was demonstrated by a bioequivalence study in 28 healthy humans with 75 mg oseltamivir phosphate capsules (Tamiflu®). Sodium fluoride (2.4 mg/mL) with potassium oxalate (3 mg/mL) was used as anticoagulant within sampling of trial. The assay reproducibility was established by reanalysis of 80 incurred samples.
Topics: Antiviral Agents; Chromatography, High Pressure Liquid; Humans; In Vitro Techniques; Limit of Detection; Oseltamivir; Reproducibility of Results; Tandem Mass Spectrometry; Therapeutic Equivalency
PubMed: 27002612
DOI: 10.1007/s00216-016-9483-2 -
Yonsei Medical Journal Jul 2017Peramivir is the first intravenously administered neuramidase inhibitor for immediate delivery of an effective single-dose treatment in patients with influenza. However,... (Comparative Study)
Comparative Study Meta-Analysis Review
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. MEDLINE, EMBASE, and Cochrane Central Register were searched for relevant clinical trials.
RESULTS
A total of seven trials [two randomized controlled trials (RCTs) and five non-randomized observational trials] involving 1676 patients were finally analyzed. The total number of peramivir- and oseltamivir-treated patients was 956 and 720, respectively. Overall, the time to alleviation of fever was lower in the peramivir-treated group compared with the oseltamivir-treated group [mean difference (MD), -7.17 hours; 95% confidence interval (CI) -11.00 to -3.34]. Especially, pooled analysis of observational studies (n=4) and studies of outpatients (n=4) demonstrated the superiority of the peramivir-treated group (MD, -7.83 hours; 95% CI -11.81 to -3.84 and MD, -7.71 hours; 95% CI -11.61 to -3.80, respectively). Mortality, length of hospital stay, change in virus titer 48 hours after admission, and the incidence of adverse events in these patients were not significantly different between the two groups.
CONCLUSION
IV peramivir therapy might reduce the time to alleviation of fever in comparison with oral oseltamivir therapy in patients with influenza; however, we could not draw clear conclusions from a meta-analysis because of the few RCTs available and methodological limitations.
Topics: Acids, Carbocyclic; Administration, Intravenous; Administration, Oral; Antiviral Agents; Cyclopentanes; Guanidines; Humans; Influenza, Human; Odds Ratio; Oseltamivir; Publication Bias; Randomized Controlled Trials as Topic; Risk Factors; Treatment Outcome
PubMed: 28540991
DOI: 10.3349/ymj.2017.58.4.778 -
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 -
Influenza and Other Respiratory Viruses Sep 2021Oseltamivir treatment is currently the only way of managing influenza in young infants for whom influenza vaccines are not licensed, but little data exist on the...
BACKGROUND
Oseltamivir treatment is currently the only way of managing influenza in young infants for whom influenza vaccines are not licensed, but little data exist on the effectiveness of the treatment in this age group.
METHODS
In a prospective study, we enrolled 431 newborn infants and followed them up for 10 months during their first respiratory season (September 2017-June 2018). During each respiratory illness, we examined the infants and obtained nasopharyngeal specimens for determination of the viral etiology. Infants with influenza were re-examined at short intervals, and additional nasopharyngeal specimens were obtained at each visit for measuring the viral load. All infants with symptoms <48 hours received oseltamivir treatment. The parents filled out daily symptom diaries.
RESULTS
Among 23 infants with influenza A, the mean total duration of illness in oseltamivir recipients was 82.1 hours, compared with 253.5 hours in infants without treatment (P = .0003). For infants with influenza B, the corresponding durations were 110.0 and 173.9 hours, respectively (P = .03). In infants with influenza A, total symptom scores were significantly lower in oseltamivir-treated infants at all time points between days 3 and 11 after the onset of therapy. In most children with either influenza A or B, viral antigen concentrations declined rapidly within 1-2 days after the initiation of oseltamivir treatment.
CONCLUSIONS
Oseltamivir treatment of infants with influenza rapidly decreased the viral load in nasopharyngeal secretions and shortened the duration and severity of symptoms. The clinical effectiveness of oseltamivir appeared to be greater against influenza A than against influenza B infections.
Topics: Antiviral Agents; Child; Humans; Infant; Infant, Newborn; Influenza Vaccines; Influenza, Human; Oseltamivir; Prospective Studies; Treatment Outcome
PubMed: 33939270
DOI: 10.1111/irv.12862 -
Current Reviews in Clinical and... 2022Several studies reported that abnormal behavior was noted in pediatric patients receiving several drugs, including neuraminidase inhibitors (NIs). However, the...
BACKGROUND
Several studies reported that abnormal behavior was noted in pediatric patients receiving several drugs, including neuraminidase inhibitors (NIs). However, the information on drugs associated with abnormal behavior in a real-world setting remains limited. The purpose of this study was to clarify the drugs associated with abnormal behavior using a spontaneous reporting system database.
METHODS
We performed a retrospective pharmacovigilance disproportionality analysis using the Japanese Adverse Drug Event Report database. Adverse event reports submitted to the Pharmaceuticals and Medical Devices Agency were analyzed, and the reporting odds ratio at 95% confidence interval were calculated.
RESULTS
A total of 1,144 reports of abnormal behavior were identified. The signals were detected through the association of 4 neuraminidase inhibitors (oseltamivir, zanamivir, laninamivir, and peramivir) with the abnormal behaviour. These signals were stronger for oseltamivir than other neuraminidase inhibitors. The signals were also detected for acetaminophen and montelukast.
CONCLUSION
Our results should be able to raise physicians' awareness of drugs associated with abnormal behavior, but further investigation of these medications is warranted.
Topics: Child; Drug-Related Side Effects and Adverse Reactions; Humans; Oseltamivir; Pharmacovigilance; Retrospective Studies; Zanamivir
PubMed: 33588740
DOI: 10.2174/1574884716666210215104540 -
Antiviral Therapy Apr 2022John Martin's untimely death in March 2021 was a huge loss for us personally, Gilead Sciences, the company he built over 30 years and the scientific community concerned...
John Martin's untimely death in March 2021 was a huge loss for us personally, Gilead Sciences, the company he built over 30 years and the scientific community concerned with antiviral therapies. We wish to honor John's legacy by retelling the discovery and history of Tamiflu and his contributions to it. Without his vision, persistence, and keen eye for opportunities, Tamiflu would not exist and Gilead's path would not have been the same. His strategic thinking around the first oral flu drug is still quite relevant today, when we are still in the SARS-CoV-2 pandemic. John explained it simply in an interview with the Science History Institute in May 2020: "…".
Topics: Humans; Influenza, Human; Oseltamivir; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35499178
DOI: 10.1177/13596535211067598 -
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 -
Clinical Microbiology and Infection :... Mar 2015
Review
Topics: Antiviral Agents; Enzyme Inhibitors; Humans; Influenza A virus; Influenza, Human; Information Dissemination; Neuraminidase; Oseltamivir; Treatment Outcome
PubMed: 25716982
DOI: 10.1016/j.cmi.2015.01.014 -
Lancet (London, England) Sep 2015
Topics: Antiviral Agents; Humans; Influenza, Human; Oseltamivir; Randomized Controlled Trials as Topic
PubMed: 26461901
DOI: 10.1016/S0140-6736(15)00203-2 -
Lancet (London, England) Sep 2015
Topics: Antiviral Agents; Humans; Influenza, Human; Oseltamivir; Randomized Controlled Trials as Topic
PubMed: 26461899
DOI: 10.1016/S0140-6736(15)00202-0