ABSTRACT
Objective: To determine the bioequivalence of two oral formulations of paracetamol 500 mg/ibuprofen 200 mg. Tolerability of both formulations of paracetamol/ ibuprofen were evaluated descriptively. Material and/or methods: Twenty-four healthy volunteers were enrolled at this random, single-dose, crossover, two-period design, open-label, bioequivalence study. After overnight fasting, two formulations (test and reference) of paracetamol/ibuprofen (paracetamol 500 mg/ ibuprofen 200-mg film coated tablets), were administered as a single dose on two treatment days separated by a 72 h (minimum) washout period. After dosing, blood samples were drawn for a period of 12 h. Pharmacokinetic parameters were determined from plasma concentrations for both formulations. The coronavirus disease 2019 (COVID-19) pandemic was declared a public health emergency of international concern by the WHO. Extraordinary safety measures were implemented at different levels that intended to preserve the clinical trial activities as far as possible, protecting the safety and preserving the traceability while no vaccine was available. These measures, locally, consisted of: information about the importance of the measures, PCR test for COVID-19 at the screening visit (if IgG serology was positive) and PCR test at every period of admission to Trials Unit, the subject came into the Unit only after a negative result. Results: The highest effort made to assure the safety of participants led to a regular development of the study, with only two cases excluded primarily and one excluded after the first dose administration. Regarding pharmacokinetics, the results found for Paracetamol: Ln (Cmax) ng/ml Ratio 92.83% (CI90: 83.73%-102.94%);Ln (AUClast) h∗ng/ml Ratio: 96.14% (CI90: 93.24%-99.13%);for Ibuprofen: Ln (Cmax) ng/ml Ratio: 93.78% (CI90: 85.43-102.96%), Ln (AUClast) h∗ng/ml Ratio: 96.06% (CI90: 93.75%-98.42%). No drug-related safety concerns appeared. Conclusions: The clinical development of the BE clinical trial was made available by the extraordinary safety measures adopted. The pharmacokinetics results comply with the regulatory requirements for bioequivalence. No significant findings concerning safety were found.
ABSTRACT
Objectives: to describe our experienced incidence, prognosis and management of hospitalized COVID-19 patients with peripheral arterial thrombosis in a major teaching hospital in Madrid (Spain). Material and methods: we designed an observational cohort study of confirmed (PCR-test) COVID-19 patients at the Hospital Universitario 12 de Octubre.We analyzed all symptomatic periheral arterial thrombosis diagnosed and treated during March and April 2020, which corresponds to the first wave of the pandemic. All elective scheduled surgery was canceled during this period due to absence of postoperative intensive care unit (ICU) or resuscitation beds and only urgent surgeries were performed. Results: from March 1 to April 30, 2,943 COVID-19 patients were admitted in our hospital and 261 patients in the intensive care unit (ICU). During this period, 154 urgent operations were performed on COVID-19 patients in our hospital. Fourteen COVID-19 patients were diagnosed with symptomatic peripheral arterial thrombosis. The average age was 74 (range, 50-92) and these events were more common in men than in women (12:2). Out of these 14 patients, only 7 underwent vascular surgery by acute limb isc hernia. This represented 4.5 %of all urgent operations performed in our hospital. Postoperative mortality was 4 of 7 patients due to re-thrombosis despite anticoagulation. Among the non-operated patients, 2 had floating aortic thrombus and evolved satisfactorily with anticoagulation, while the other 5 patients were managed by palliatives measures due to the poor clinical conditions until they died. No analytical parameter was predictive of arterial thrombosis. No bleedings were recorded in this series. Conclusions: the surgical trauma increased the vulnerability of these patients with COVID-19, and therefore, surgery should be avoided whenever possible. The mortality rate in vascular surgery was dramatically high. The high thrombogenicity of these patients discourages bypass or other revascularization procedures. All hospitalized COVID-19 patients should receive a ntithrombotic prophylaxis with low molecular weight heparin (LMWH), and those at high risk should be fully anti coagulated.