Background: High values of endogenous levels of magnesium (Mg) in the body and mechanisms of homeostasis regulation make it difficult to assess the bioavailability of these drugs. The aim of this study was to assess the Mg concentration in blood in volunteers and in erythrocytes in patients with hypomagnesemia.Methods: The study included 20 healthy volunteers and 62 patients with chronic heart failure (CHF) I–III functional class (FC) NYHA classification. We studied the composition of Mgorotate and Mgorotate plus potassium (К)orotate. Blood sampling was carried out at 8 a.m. and within 10 h after administering the drugs. Measurement of Mg pharmacokinetic parameters: AUC (concentration of the active substance-time), and Cmax (maximum concentration) in volunteers and measurement of the concentration of Mg in erythrocytes of patients.Results: The results indicated that both the AUC in volunteers and concentration of Mg in erythrocytes of patients are comparable, and the differences are not statistically significant.Conclusions: The study showed that the standard method of calculating the AUC (total serum Mg) is insufficient for comparative evaluation of Mg absorption due to the high levels of its endogenous content and a small increase in concentration after taking the drugs. It is advisable to assess the concentration of Mg in the red blood cells of patients.

Рассмотрены требования FDA к валидации биоаналитических методик, опубликованные в новом руководстве 2018 г., необходимые для подтверждения их надежности для определения концентрации анализируемого вещества. Кратко описана история регулирования валидации биоаналитических методик. Представлен обзор ключевых изменений и дополнений руководства FDA по валидации биоаналитических методик, которые включают в себя объединение требований к валидации хроматографических методик и методик связывания лиганда, указание на валидацию биомаркеров, выделение раздела, посвященного новым технологиям (например, методу сухой капли крови), введение концепции соответствия поставленным целям. Проведено сравнение требований к валидационным параметрам хроматографических методик руководства FDA и требований ЕАЭС. Несмотря на некоторые отличия, как в количестве параметров, так и в критериях их приемлемости, требования нового руководства FDA в целом согласуются с документом ЕАЭС.

Iron deficiency remains one of the most common deficiencies worldwide. An inadequate and unbalanced diet may cause a lack of other nutrients necessary for hematopoiesis, which increases the risk of iron deficiency and makes it difficult to treat. Various pharmacotherapeutic approaches are being studied and applied, including combination medications, which in addition to iron consist of folic acid, copper/manganese gluconate, ascorbic acid, multivitamins, serine, and cyanocobalamin. Folate is a component that affects both the efficacy and safety of pharmacotherapy for iron deficiency. Preclinical animal studies comparing the dynamics of hematological indices confirmed a more rapid achievement of target values with the simultaneous use of iron and folic acid. Clinical studies in a group of pregnant women with iron-deficiency anemia (IDA) demonstrated that folic acid in combination with iron was more effective than iron as monotherapy. The combination of iron and folic acid is also rational in terms of increasing safety: folic acid prevents iron accumulation in the liver and the associated development of fibrosis. Ironinduced liver injury is related to oxidative stress catalyzed by iron overload. Folic acid regulates the transcription of genes involved in oxidative stress in the liver and the activity of 5'-AMP-activated protein kinase. Key words: iron deficiency, folic acid, hematopoiesis, rational pharmacotherapy

Показано, что исследование биоэквивалентности воспроизведенных препаратов, действующие вещества которых эквивалентны эндогенным соединениям, присутствующим в организме человека в фоновых концентрациях, является сложной задачей и требует особого регуляторного подхода по сравнению с другими препаратами. При отсутствии общедоступных научных данных в отношении того, что прием препарата может повышать общее содержание эндогенного вещества, проведение исследования биоэквивалентности может стать экономически нецелесообразным в сравнении со стандартным сравнительным клиническим исследованием, так как потребуется сначала подтвердить значимость повышения его концентрации в плазме крови. Проанализированы требования российского законодательства и международного права к оценке лекарственных препаратов, являющихся аналогами эндогенных соединений, таких как витамины, гормоны, ферменты, аминокислоты, соли. Показано, что для получения объективных результатов исследования биоэквивалентности необходимо проводить коррекцию на эндогенную концентрацию вещества в плазме крови и контроль его поступления с пищей. Обобщен опыт проведения экспертизы ФГБУ «НЦЭСМП» Минздрава России в отношении препаратов — аналогов эндогенных соединений. Выявлены наиболее частые ошибки при подготовке протоколов исследований. Обоснована необходимость индивидуального подхода для каждого конкретного препарата, так как эталонного решения проблемы фонового содержания эндогенных соединений не существует. Выработаны некоторые ключевые положения, которые помогут минимизировать влияние фоновых концентраций исследуемых веществ в организме на результаты оценки биоэквивалентности. Определены основные пути для разрешения проблем, сформулированных на основании проведенного анализа и опыта экспертизы.

Pharmacotherapy for allergic rhinitis is based on different categories of drugs used either in monotherapy or in combination regimens. The current clinical guidelines suggest a stepwise approach to pharmacotherapy for allergic rhinitis. The use of intranasal corticosteroids is considered as the preferred second-stage pharmacotherapy. Inadequate control of AR symptoms in first-line therapy is a common problem. Integrated care pathways (ICP), developed taking into account the data obtained about patients using a mobile application, suggest the use of intranasal corticosteroids as the first line of therapy, including in patients with intermittent rhinitis who have not previously received treatment when assessing the condition according to the VAS for more than 5 points, in patients who received earlier treatment when assessing the condition according to the VAS less than 5 points. According to the data in the medical decision support system and continuing medical education UpToDate, inhaled corticosteroids are considered as the first-line drugs for the pharmacotherapy of allergic rhinitis. In terms of pharmacodynamic efficacy, intranasal corticosteroids are comparable to each other. The selection criteria can be considered: the value of systemic absorption; lipophilicity; the start time of the action; frequency of introduction, organoleptic properties; the possibility of influencing non-nasal symptoms. The use of sprays containing both a glucocorticoid and an antihistamine (mometasone furoate/azelastine hydrochloride) opens up additional pharmacotherapeutic possibilities in the treatment of allergic rhinitis.

Helicobacter pylori infection can serve as one of indications to clarithromycin prescription. H. pylori eradication is performed commonly as a treatment for diseases caused by this pathogen and conditions with an increased risk of complications (precancerous changes of the gastric mucosa, unspecified iron deficiency anemia, idiopathic thrombocytopenic purpura, long-term NSAIDs use, anti-platelet drugs use etc). A number of H. pylori functional characteristics determines specific requirements for eradication schemes: high sensitivity of the pathogen, the ability of antibacterial drugs to penetrate and accumulate in gastric tissue and mucous,a stimulation of microorganism’s reproduction and protection of acid-resistant drugs by reducing gastric acid production as well. If the latter is provided by the use of proton pump inhibitors, then clarithromycin fully provides the other issues above. In Russia, standard triple therapy is used as the first-line treatment of H. pylori infection due to current clarithromycin resistance less than 15%. The article gives detailed reasoning and factual evidence of commitment to the first-line therapy under the increasing prevalence of the most recent antibiotic resistance (local resistance to levofloxacin has reached 20%), the high potential for multi-drug resistant H. pylori strains appearing, low ensuring medical facilities with relevant resistance test-systems, a role of generic drugs (clarithromycin and proton pump inhibitors) with compromised pharmaceutical characteristics in creation and erroneous interpretation of a pseudoresistance to clarithromycin.