Изучение влияния приёма пищи на биодоступность, безопасность и переносимость лекарственного препарата Атериксен®, таблетки, 100 мг у здоровых добровольцев

The aim. The primary objective of the study was to evaluate the effect of food on the bioavailability of Aterixen® 100 mg tablet after single oral dose under fasting or fed conditions. The secondary objective was to evaluate the pharmacokinetic parameters, safety, and tolerability of Aterixen® 100 mg tablet after single oral dose under fasting or fed conditions. Materials and methods. Healthy male and female volunteers aged 18 to 45 years were included in the study. Due to lack of data about intra-individual variability of the main pharmacokinetic parameters of the active substance in Aterixen® (XC221GI, 1-[2-(1-Methylimidazol-4-yl)-ethyl]perhydroazin-2,6-dione), an adaptive group sequential approach was used in the study. At Stage I, 24 volunteers were randomized into 2 groups (12 in each group): Group 1 (sequence AAB) received treatment A (administration of the drug under fasting conditions) during period I, treatment A during period II and treatment B (administration of the drug under fed conditions) during period III, Group 2 (sequence BBA) received therapy B during period I, therapy B during period II, and therapy A during period III. In each study period, serial blood samples were collected before and throughout 12 h after administration of the study drug. The quantification of the active substance XC221GI in plasma samples was performed using a validated high-performance liquid chromatography method with mass spectrometric detection. Safety evaluation was performed on the basis of frequency and severity of adverse events (AEs) and serious adverse events (SAEs), which were registered based on complaints, physical examination, laboratory tests, and electrocardiography (ECG). Drug tolerability was evaluated in terms of proportion of volunteers who prematurely discontinued participation in the study due to AE/SAE. Results. 24 randomized volunteers completed the study in compliance with the approved study protocol. The averaged pharmacokinetic curves profiles of XC221GI had similar shapes under fasting and fed conditions. Confidence intervals for the ratio of the geometric means for the primary parameters (AUC(0-t) and Cmax) of XC221GI and AUC(0-∞) were within the 80-125 % acceptance interval, while a small in absolute value, but statistically significant differences were noted in time until Cmax is reached. Throughout the study, 2 volunteers reported AEs (low RBC count, low hemoglobin concentration, and low hematocrit value) after receiving the study drug under fed conditions. All reported AEs were mild. The relationship between AEs and the study drug product was assessed by investigator as doubtful. Conclusion. The results of this study indicate that food does not affect the bioavailability of Aterixen® 100 mg, tablets, and the single oral dose of 100 mg was safe and well tolerated by healthy volunteers.Цель исследования. Первичной целью исследования являлась оценка влияния приёма пищи на биодоступность лекарственного препарата Атериксен®, таблетки, 100 мг после его однократного приёма натощак и после еды. Дополнительная цель заключалась в оценке фармакокинетических параметров, безопасности и переносимости препарата Атериксен® при его однократном приёме в дозе 100 мг натощак и после приёма пищи. Материал и методы. В исследование включали здоровых добровольцев мужского и женского пола в возрасте от 18 до 45 лет. В связи с отсутствием данных о внутрииндивидуальной вариабельности основных фармакокинетических параметров действующего вещества препарата Атериксен® (XC221GI, 1-[2-(1-Метилимидазол-4-ил)-этил]пергидроазин-2,6-дион) в исследовании применялся адаптивный последовательный подход. На Этапе I было рандомизировано 24 добровольца (по 12 в каждой группе): группа 1 (последовательность ААВ) принимала терапию А (приём препарата натощак) в периоде I, терапию А в периоде II и терапию В (приём препарата после еды) в периоде III, группа 2 (последовательность ВВА) принимала терапию В в периоде I, терапию В в периоде II и терапию А в периоде III. В каждом периоде исследования у добровольцев отбирали образцы крови до и в течение 12 ч после приёма препарата исследования. Количественное определение действующего вещества XC221GI в образцах плазмы крови проводилось валидированным методом высокоэффективной жидкостной хроматографии с масс-спектрометрическим детектированием. Безопасность препарата оценивали по количеству и степени тяжести нежелательных явлений (НЯ) и серьёзных нежелательных явлений (СНЯ), зарегистрированных на основании жалоб, данных физикального осмотра, а также по изменениям лабораторных показателей и электрокардиографического исследования (ЭКГ). Переносимость исследуемого препарата оценивали по доле добровольцев, досрочно прекративших участие в исследовании из-за возникновения НЯ/СНЯ. Результаты исследования. 24 рандомизированных добровольца завершили исследование полностью в соответствии с одобренным протоколом исследования. Усреднённые профили фармакокинетических кривых XC221GI при приёме исследуемого препарата натощак и после приёма пищи имели близкие формы. Доверительные интервалы для отношений средних геометрических значений первичных показателей (AUC(0-t) и Cmax) XC221GI, а также AUC(0-∞) соответствовали пределам эквивалентности 80,00–125,00 %, при этом было отмечено небольшое по абсолютной величине, но статистически значимое различие по времени достижения максимальной концентрации исследуемого вещества. На протяжении исследования у 2 добровольцев при приёме препарата после приёма пищи отмечались НЯ в виде снижения количества эритроцитов, концентрации гемоглобина и значения гематокрита. Все зарегистрированные НЯ имели лёгкую степень тяжести. Связь НЯ с исследуемым препаратом по оценке врача-исследователя была расценена как сомнительная. Заключение. Результаты исследования показали отсутствие влияния фактора приёма пищи на биодоступность лекарственного препарата Атериксен®, таблетки, 100 мг, а также его безопасность и хорошую переносимость при однократном приёме здоровыми добровольцами в дозе 100 мг

Microbiological and epidemiological features of microbial associations in septic infections in surgical departments

Introduction: The problem of septic infections (SI) is still an actuality, despite the positive developments in the fight against infectious diseases Objective: The study of the microbiological and epidemiological characteristics of poly etiology of purulent-septic infections in surgical patient's general hospital Materials and methods: Isolation and identification of microorganisms was carried out by conventional methods. To identify clinical and epidemiological features performed a retrospective analysis of incidence, according to official registration in the recording and reporting hospital. Results: 108 strains of microorganisms were aallocated, belonging to the 11 species. Among Assiociants dominated by Staphylococcus aureus (35,18%), Acinetobacter baumannii and Staphylococcus epidermidis. Acinetobacter baumannii and Staphylococcus epidermidis predominated, and among Assiociants among monocultures. Enterobacter agglomerans, Proteus mirabilis recorded only in the association. For surgical patients the most frequent combination of established S.aureus, Staphylococcus epidermidis among themselves, as well as E.coli, Proteus spp., Entero-coccus spp. Most species of microorganisms occurred mainly in the form of associations. In general surgery the figure was equal to 64.3%, dominated by two-component association. The number of multidrug-resistant crops amounted to 25,1% (Acinetobacter baumannii, Staphylococcus aureus, Enterobacter agglomerans). Jaccard coefficient was highest for Staphylococcus aureus Staphylococcus epidermidis (68,9%) and Staphylococcus aureus c Acinetobacter baumannii (47,5%), which corresponds to the synergistic relationship. And in the associations and Staphylococcus epidermidis Acinetobacter koeffitsient 17.1 - has an antagonist relationship. The neutral attitude prevailed over the synergistic and antagonistic. The average incidence of polyetiology infections was 17 per 100. As a result of the study, the following clinical and epidemiological features of polyetiology of infections in surgical patients and risk factors for their development: the leading pathology in polyetiology infections - skin and subcutaneous tissue (70%). The age structure of patients was predominantly older age group (42 to 60), and the average age of the patients was 54. The main type of surgery - opening abscesses, phlegmon, limbs amputation. Poly etiology of infections in patients had more surgical interventions (70.1%) and it was found that more patients with infections were poly etiology necrectomy. Duration of hospital stay was 13.4 days on average. The intensity of the ABT was primarily a course. Conclusions: Organization of the microbiological monitoring of poly-etiology SI, is a necessary part of the surveillance of hospital infections

Virtual Dike and Flood Simulator: Parallel distributed computing for flood early warning systems *

The paper presents two simulation modules –Virtual Dike and Flood Simulator – developed for flood Early Warning Systems (EWS). The UrbanFlood EWS is a distributed system that (1) analyzes sensor data received in real-time from flood defenses (dikes, dams, etc.) and (2) simulates dike stability, breaching and flood propagation. Computational modules are invoked by workflow-based expert scenarios via the Common Information Space middleware. The Virtual Dike and Flood Simulator have been ported to the HPC Cloud system of SARA supercomputing centre in Amsterdam. Cloud system provides dynamic resource allocation and remote user control. Virtual Dike is a parallel FSI module for coupled simulation of porous flow and dike deformation, based on the finite element method. Efficiency of the distributed EWS and solver parallel performance are presented. 1