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1.
Electroanalysis ; : 8, 2022.
Article in English | Web of Science | ID: covidwho-1680319

ABSTRACT

During COVID-19 pandemic, coagulopathy have been reported as a potential threat to most infected patients. Edoxaban (EDX) is a direct oral anticoagulant that is recently added to most COVID-19 treatment protocols either as therapy or prophylaxis. Herein, a novel nanoparticles modified glassy carbon potentiometric sensor was developed for the selective quantitation of EDX in human plasma. The electrochemical performance of the proposed sensor was assessed and compared to nanoparticle free sensor. An enhancement in electrode performance including: detection limit (3.39 x 10(-6) mol L-1), response time (8.0 +/- 2.0 s) and improved selectivity. The proposed sensor was able to determine EDX in pure form, pharmaceutical formulation and human plasma.

2.
Italian Journal of Medicine ; 15(3):12, 2021.
Article in English | EMBASE | ID: covidwho-1567335

ABSTRACT

Background: Venous thromboembolism, arterial thrombosis and thrombotic microangiopathy substantially contribute to increased morbidity and mortality in CoViD-19. We report a case of 56-year old man that presented with stroke and was found to have CoViD- 19 pneumonia complicated by pulmonary embolism (PE). Description of the case: A 55-year-old man with history of hypertension presented to the emergency department after a transient loss of consciousness. He was found to have left lateral hemianopia and lower right quadrantanopsia and head CT confirmed bilateral stroke in the posterior cerebral artery territory. MR angiography excluded atherosclerosis/dissection of the vertebral and basilar artery and a positive nasopharingeal swab PCR test revealed SARS-CoV-2 infection. The patient was admitted and ASA 100 mg and enoxaparin 40 mg per day were started. He experienced dry cough and fever and 10 days after admission presented atypical chest pain. CT Angiography revealed multiple confined ground glass opacities with segmental bilateral PE. Therapeutic dose of enoxaparin was started and after 5 days switched to edoxaban 60 mg per day. The patient progressively recovered and a complete work up excluded patent foramen ovale and any other cause predisponing to combined presence of venous and arterial thrombosis Conclusions: CoViD-19 has presented many diagnostic challanges in patients with neurologic and respiratory findings: thromboembolic disease may even be the initial or unique presentation. The early recognition of these phenotipes of the disease play a dramatic role in the CoViD-19 management.

3.
Int J Pharm ; 608: 121122, 2021 Oct 25.
Article in English | MEDLINE | ID: covidwho-1433361

ABSTRACT

Herein, we demonstrated the development and characterization of a dry powder inhaler (DPI) formulation of edoxaban (EDX); and investigated the in-vitro anticoagulation effect for the management of pulmonary or cerebral coagulopathy associated with COVID-19 infection. The formulations were prepared by mixing the inhalable micronized drug with a large carrier lactose and dispersibility enhancers, leucine, and magnesium stearate. The drug-excipient interaction was studied using X-Ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) methods. The drug and excipients showed no physical inter particulate interaction. The in-vitro drug aerosolization from the developed formulation was determined by a Twin Stage Impinger (TSI) at a flow rate of 60 ± 5 L /min. The amount of drug deposition was quantified by an established HPLC-UV method. The fine particle fraction (FPF) of EDX API from drug alone formulation was 7%, whereas the formulations with excipients increased dramatically to almost 7-folds up to 47%. The developed DPI formulation of EDX showed a promising in-vitro anticoagulation effect at a very low concentration. This novel DPI formulation of EDX could be a potential and effective inhalation therapy for managing pulmonary venous thromboembolism (VTE) associated with COVID-19 infection. Further studies are warranted to investigate the toxicity and clinical application of the inhaled EDX DPI formulation.


Subject(s)
Blood Coagulation Disorders/drug therapy , COVID-19 , Dry Powder Inhalers , Pyridines/administration & dosage , Thiazoles/administration & dosage , Administration, Inhalation , Aerosols , Blood Coagulation Disorders/virology , COVID-19/complications , Humans , Particle Size , Powders
4.
Expert Rev Clin Pharmacol ; 14(10): 1289-1294, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1360277

ABSTRACT

PURPOSE: We aimed to investigate the clinical performance of edoxaban for the treatment of pulmonary embolism (PE) in hospitalized COVID-19 patients. METHODS: We conducted a retrospective analysis selecting hospitalized patients with COVID-19 admitted to our Institution from 20 May 2020 to 20 November 2020 with computer tomography (CT) detected PE at admission, treated with edoxaban after initial parenteral therapy. Clinical outcomes were compared between patients with and without ARDS at admission and between those with and without CT confirmed PE resolution. RESULTS: 50 patients were included. Mean follow-up was 42.5 ± 10 days. No baseline differences were found between patients with ARDS (30%) and those without ARDS at admission. Patients with PE resolution (84%) were younger (P = 0.03), had a shorter duration of fondaparinux therapy (9.9 ± 3.8 vs 15.8 ± 7.5 days; P = 0.0015) and length of hospitalization (36 ± 8 vs 46 ± 9 days: P = 0.0023) compared with those without PE resolution. 2 patients experienced major bleedings. At multivariate analysis the time to edoxaban switch was the only predictor of the PE resolution (HR: 0.92; 95% C.I. 0.86 to 0.99). CONCLUSION: Edoxaban was an effective and safe treatment for acute PE in COVID-19 setting.


Subject(s)
COVID-19/complications , Factor Xa Inhibitors/therapeutic use , Pulmonary Embolism/drug therapy , Pyridines/therapeutic use , SARS-CoV-2 , Thiazoles/therapeutic use , Adult , Aged , Female , Fondaparinux/therapeutic use , Humans , Male , Middle Aged , Multivariate Analysis , Proportional Hazards Models , Pulmonary Embolism/etiology , Respiratory Distress Syndrome , Retrospective Studies
5.
Biomedicines ; 9(5)2021 Apr 22.
Article in English | MEDLINE | ID: covidwho-1202388

ABSTRACT

Dabigatran, rivaroxaban, apixaban, and edoxaban are direct oral anticoagulants (DOACs) that are increasingly used worldwide. Taking into account their widespread use for the prevention of thromboembolism in cardiology, neurology, orthopedics, and coronavirus disease 2019 (COVID 19) as well as their different pharmacokinetics and pharmacogenetics dependence, it is critical to explore new opportunities for DOACs administration and predict their dosage when used as monotherapy or in combination with other drugs. In this review, we describe the details of the relative pharmacogenetics on the pharmacokinetics of DOACs as well as new data concerning the clinical characteristics that predetermine the needed dosage and the risk of adverse drug reactions (ADRs). The usefulness of genetic information before and shortly after the initiation of DOACs is also discussed. The reasons for particular attention to these issues are not only new genetic knowledge and genotyping possibilities, but also the risk of serious ADRs (primarily, gastrointestinal bleeding). Taking into account the effect of the carriership of single nucleotide variants (SNVs) of genes encoding biotransformation enzymes and DOACs metabolism, the use of these measures is important to predict changes in pharmacokinetics and the risk of ADRs in patients with a high risk of thromboembolism who receive anticoagulant therapy.

6.
J Clin Neurosci ; 79: 30-32, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-665630

ABSTRACT

COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was first reported in Wuhan, China in December 2019, and is ongoing pandemic. While a majority of patients with SARS-CoV-2 infection shows asymptomatic or mild disease, hospitalized patients can develop critical condition, such as pneumonia, sepsis, and respiratory failure. Some cases deteriorate into sever systemic disease and multiorgan failure. Many patients of severe COVID-19 show hypercoagulable state and complicate with venous thromboembolism and atrial thrombosis. We herein reported a case of COVID-19 who developed cerebral venous thrombosis (CVT) co-incidence with pulmonary thromboembolism (PTE). A 56-year-old Japanese man was presented with fever and malaise and diagnosed with COVID-19. He was treated with ciclesonide and azithromycin, but his respiratory condition deteriorated. Thus, systemic corticosteroids and favipiravir were initiated and these treatments resulted in afebrile state, improving malaise and respiratory failure. However, he suddenly developed severe headache and vomiting with increased concentration of D-dimer. Brain CT and MRI showed typical images of CVT in the left transvers sinus and CT pulmonary angiography showed PE. Administration of unfractionated heparin followed by edoxaban treatment reduced the levels of D-dimer and improved his clinical presentation and thrombosis. Monitoring coagulopathy is important in COVID-19 patients and in case of venous thromboembolism, including cerebral venous system, appropriate anticoagulant therapy should be initiated.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Intracranial Thrombosis/etiology , Pneumonia, Viral/complications , Venous Thrombosis/etiology , COVID-19 , Fibrin Fibrinogen Degradation Products/analysis , Heparin/therapeutic use , Humans , Intracranial Thrombosis/diagnostic imaging , Intracranial Thrombosis/drug therapy , Magnetic Resonance Imaging , Male , Middle Aged , Pandemics , Pyridines/therapeutic use , SARS-CoV-2 , Thiazoles/therapeutic use , Tomography, X-Ray Computed , Venous Thrombosis/diagnostic imaging , Venous Thrombosis/drug therapy
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