Pharmacokinetics of two amitriptyline tablets, Amitryptiline Nycomed and Amitryptiline, was investigated clinically and experimentally after a single oral dose of 50 mg. A statistically significant correlation between amitryptiline serum concentrations in dogs and healthy humans (r=0.683, p<0.006) was established. In humans, standartized values of peak concentration and area under the concentration curve were significantly higher, specific volume of distribution and total clearance were lower, and half-life and mean retention time were significantly higher than in dogs. Characteristics of apparent bioavailability in dogs and healthy people did not statistically differ.

Objectives To study the pharmacokinetics and relative bioavailability of drugs of different chemical structure and pharmacological action under conditions simulating the effects of some factors of spaceflight, as well as the peculiarities of the pharmacokinetics of acetaminophen under long-term spaceflight conditions. Methods The pharmacokinetics of verapamil (n=8), propranolol (n=8), etacizine (n=9), furosemide (n=6), and acetaminophen (n=7) in healthy volunteers after a single oral administration under normal conditions (background) and under antiorthostatic hypokinesia (ANOH), the pharmacokinetics of acetaminophen in spaceflight members under normal ground conditions (background) (n=8) and under prolonged spaceflight conditions (SF) (n=5) were studied. Results The stay of volunteers under antiorthostatic hypokinesia had different effects on the pharmacokinetics and bioavailability of drugs: Compared to background, there was a decreasing trend in Vz for verapamil (−54 Δ%), furosemide (−20 Δ%), propranolol (−8 Δ%), and acetaminophen (−9 Δ%), but a statistically significant increase in Vz was found for etacizine (+39 Δ%); there was an increasing trend in Clt for propranolol (+13 Δ%) and acetaminophen (+16 Δ%), and a decreasing trend in Clt for etacizine, verapamil, and furosemide (−22, −23 and −9 Δ% respectively) in ANOH. The relative bioavailability of etacizine, verapamil, and furosemide in ANOH increased compared to background (+40, +23 and +13 Δ%, respectively), propranolol and acetaminophen decreased (−5 and −12 Δ% accordingly). The relative rate of absorption of etacizine and furosemide in ANOH decreased (−19 and −20 Δ%, respectively) while that of verapamil, propranolol, and acetaminophen increased (+42, +58 and +26 Δ%, respectively). A statistically significant decrease in AUC0-∞ (−57 Δ%), Cmax (−53 Δ%), relative bioavailability of acetaminophen (−52 Δ%) and a sharp increase in Clt (+147 Δ%), Tmax (+131 Δ%) as well as a trend towards a significant decrease in T1/2 (−53 Δ%), MRT (−36 Δ%) and a moderate increase in Vz (+24 Δ%) were found under control compared to background. Unidirectional changes in AUC0-∞, Clt, T1/2, MRT and relative bioavailability of acetaminophen, which are more pronounced in SF and opposite dynamics for Cmax, Tmax, Vz were found in ANOH and SP compared to background studies. Conclusions The data obtained allow recommending the studied drugs for rational pharmacotherapy in the possible development of cardiovascular disease in manned spaceflight.

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Background: Factor Xa (FXa) is known to play a central role in blood coagulation cascade and considered to be one of the most attractive tar-gets for oral anticoagulants of new generation.Objective: Our approach for the development of directly acting oral anticoagu-lants (DOAC), FXa inhibitors was demonstrated in this work.Method: Chemical synthesis is the base of our approach for the development of potential inhibitors. In this work, the substances like R1-(CONH)-R2-(CONH)-R3 are being developed, using previously described docking and screening meth-ods, where R1, R2 and R3 are some chemical groups and (CONH) are amide bonds connecting R1, R2 and R3. The direction of amide bond (CONH) could be arbitrary for R1, R2 and R2, R3.Results: Chemical modifications were made in the frame of the results, taking into account the structure of FXa, chemical synthesis capabilities, as well as pa-tentability of the target compounds. Subnanomolar potency of several devel-oped compounds was achieved. Several analyzers and various testing-suites have been used to measure the concentration that doubled the prothrombin time (PTx2). Moreover, in human plasma the PTx2 concentration of the compound 217 (DD217) turned out to be 80±20 nM. The compound efficacy has proved by in vivo assays including oral administrations in rats, rabbits and monkeys.Conclusion: The pharmacodynamic profile of DD217 for oral administration in cynomolgus monkeys proves the efficacy of the compound, which makes it promising for the future preclinical trials.

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Introduction. Post-graduate education of residents is the basis of the professional activity of doctors. Therapeutic activities involve emotional load and a lot of stress factors. Emotional burnout syndrome (EBS) is the response of the organism to prolonged negative exposure to professional stresses. Psychological overwork is considered to be the main cause of EBS. This article is devoted to the study of resource possibilities of the individual and to the search for ways to prevent the development of EBS in residents at the postgraduate stage of education. Materials and methods. The EBS analysis (V.V. Boyko’s method), conflict competence (method "Diagnostics of leading type of response" by M.M. Kashapov and T.G. Kiseleva), communicative competence (method "Professional communicative competence of the doctor" by N.V. Yakovleva and L.P. Urvantsev), creativity (test "Creativity" by N.F. Vishniakova) and creative characteristics of personality (Questionnaire of abilities of creative personality by O.A. Shliapnikova and M.M. Kashapov) were used to examine 130 persons (100 residents of surgical and therapeutic specialties and 30 doctors of general practice) in comparison groups with correlation analysis. Results. The obtained data support the hypothesis that 1) differences in the choice of conflict resolution strategy contribute to the development of EBS symptoms; 2) residents experience a shortage of professional communicative competence, which leads to the development of EBS; 3) there are relationships between the parameters of creativity and the expression of EBS; 4) the chosen medical specialty is related to the degree of expression of creative abilities of the individual. Discussion and conclusion. The reasons for the identified psychological disadvantage are analyzed. A comparative analysis of conflict and communication competencies, as well as creative characteristics of the person, which play a role in the development of the EBS has been carried out. It has been established that creativity and creative abilities manifest themselves as resource opportunities whose targeted development can serve as a means of preventing EBS in residents.

Introduction. Getting higher medical education in specialty and residency programs is an important stage of doctor's formation. Medical activity implies emotional intensity and a great number of factors that cause stress. Emotional burnout syndrome is not only the result of neuropsychological stress, but also the consequence of uncontrollable stress. Research aim: to determine the predictors of emotional burnout syndrome development in students of higher medical education programs (specialist and residency). Materials and methods. The sample of 330 students undergoing specialist and residency programs at Yaroslavl State Medical University of the Ministry of Health Care of Russia and 50 doctors from different medical organizations of Yaroslavl region was used as a control group to estimate their thinking styles, types of thinking and creativity as well as factors of cognitive appraisal of difficult life situations and to analyze their interrelation and impact on a burnout syndrome component. Statistical data processing was carried out using Kolmogorov-Smirnov criterion with Lillifort and Shapiro-Wilk correction, Spearman rank correlation coefficient, Mann-Whitney U-test, Student's t-criterion, Pearson's χ² test, and factor analysis (ANOVA) based on Kaiser-Meyer-Olkin test and multiple logistic regression analysis. Study Results. It was found that in all three comparison groups the practical thinking style was significantly more frequent (p≤0.05). From the types of thinking reliably more often (p≤0,05) students use figurative, residents – combined, and doctors – sign type. When analyzing the SES phases, reliable differences were found in the predominance of the frequency of occurrence of only the formed phase "Resistance" in doctors over residents (p=0,016). In a comparative analysis of more difficult situations (≥4 points) between groups, it was found that significantly more students compared to residents have common signs of difficult life situations (p=0.008), significantly more strong emotions are experienced by students compared to residents (p=0.0003) and to doctors (p=0.006). Correlation analysis showed: for students the presence of direct links of medium strength between the sign type of thinking and "strong emotions", emotional detachment and "future perspective"; for residents the presence of direct and inverse links of very weak and weak strength, which can be neglected. Factor analysis revealed the main components in each group under study that described the influence patterns of the factors of cognitive evaluation of life situations on certain burnout symptoms with the highest percentage. Conclusion. Logistic regression analysis revealed a number of cognitive evaluation factors as predictors of burnout and, vice versa, a number of burnout symptoms can act as predictors of some cognitive evaluation factors.

Consecutive completion of specialist and residency training is an important stage in the development of a young physician. Therapeutic activity implies emotional intensity and a great number of factors, causing stress. The syndrome of emotional burnout is not only a result of neuropsychological stress, but also a consequence of uncontrolled stress. The aim of the research was to determine influence of thinking styles, types of thinking and creativity level on factors of cognitive appraisal as predictors of burnout syndrome development in higher education trainees (specialist and postgraduate training programmes). The search of predictors of a burnout syndrome was carried out for a sample of 330 medical students and 50 physicians of the control group. As a result of research it has been revealed that trainees as well as practitioners have a practical style of thinking; postgraduate trainees more often use the combined one, students, figurative; and physicians, sign type of thinking; higher parameters of creativity are marked in postgraduate trainees over physicians. In general, students on specialty and postgraduate training programmes have less difficulty with most of the cognitive assessment factors. The correlation analysis showed as follows: for students, there were direct links of medium strength between the sign type of thinking and “strong emotionsˮ, emotional detachment, and “future perspectiveˮ; for postgraduate trainees, there were direct and inverse links of very weak and weak strength, which could be neglected. However, further factor analysis is required in order to assess the influence of certain factor on the development of emotional burnout syndrome in medical trainees.