Vol 24, No 6 (2018)

Goal. Сompare the effectiveness of combination therapy with zofenopril and lisinopril in patients with preserved ejection fraction (CHFpEF) of the left ventricle (LV) in the presence of hypertension disease (HD), considering its impact on the regulatory adaptive status (RAS). Material and methods. 69 patients with CHFpEF in the presence of HD III stage who were randomized into two groups for treatment with zofenopril (17,9±5,9 mg/day, n=35) or lisinopril (14,2±4,3 mg/day, n=34). As part of combination pharmacotherapy, patients were included nebivolol (6,5±1,8 mg/day and 5,8±1,7 mg/day), and acetylsalicylic acid when required (100 mg/day, n=7 and 100 mg/day, n=8), atorvastatin (16,5±4,7 mg/day, n=12 and 15,7±4,8 mg/day, n=14), respectively. Initially and after six months, the following was done: a quantitative evaluation of the RAS (by cardio-respiratory synchronism test), echocardiography, treadmill test, six-minute walking test, determination of the N-terminal precursor of the natriuretic brain peptide level in blood plasma, holter monitoring of blood electrocardiograms, all-day monitoring of pressure, subjective evaluation of quality of life. Results. Both schemes of combined therapy comparatively controlled arterial hypertension, improved functional and structural state of the heart, reduced neurohumoral activity. Compared with lisinopril, the use of zofenopril more positively influenced on RAS, increased exercise tolerance and improved quality of life. Conclusion. The use of zofenopril, in comparison with lisinopril, in patients with CHFpEF LV on the background HD of III stage is preferable due to a more positive effect on RAS.

Objective: Drug Amlodipine+Valsartan is safe and effective for comprehensive treatment of arterial hypertension patients taken combined therapy by prescription. The development of new fix drug combination amlodipine and valsartan will provide in the near future a significant reduction in the cost of treatment. The aim of this work was investigation of bioequivalence for a generic drug Amlodipine+Valsartan, film-coated tablets, 10 mg+160 mg (Polpharma SA, Poland) and Exforge®, film-coated tablets, 10 mg+160 mg (Novartis Pharma AG, Switzerland). Materials and methods: 58 healthy volunteers were enrolled in open label, randomized, two sequence, two treatment cross-over study. Drugs were administered in two periods with a 21-day washout period in-between. Blood samples were collected over a 72-hour period. Amlodipine and Valsartan were measured in plasma using an automated LC-MS/MS assay. Pharmacokinetic parameters were calculated by non-compartmental analyses approach to evaluate AUC0-t, AUC0-∞ and Cmax. ANOVA was performed on the ln-transformed data and the 90% Confidence Interval (CI) was determined. Bioequivalence will be concluded if the 90% CI falls within 80-125% for AUC0-t and Cmax. Results: 53 volunteers completed the study and were considered for the pharmacokinetic and statistical analyses. Descriptive safety data analyses were performed on all 58 subjects. 90%-CI for corrected GMEAN of test and reference ratio was 94.76-105.24% for AUC0-t and 92.78-108.79% for Cmax in the case of amlodipine; 94.93-119.61% for AUC0-t and 90.41-116.03% for Cmax in the case of valsartan. So all pharmacokinetic parameters met the acceptance criteria as the 90% CI were within 80.00-125.00%. Conclusion: This study showed that Amlodipine+Valsartan, film-coated tablets, 10 mg+160 mg (Polpharma SA, Poland) is bioequivalent to reference product Exforge®, film-coated tablets, 10 mg+160 mg (Novartis Pharma AG, Switzerland).

In recent times the question of the bidirectional interactions of the neuroendocrine and immune systems is studied quite actively, its mechanisms offer the opportunity to allow for optimization the therapy of several diseases, including Parkinson’s disease. The purpose of this work is to study the influence of peptide drugs derived from the body’s immune system, the thymus, for the avoidance test conditioning, both in health and in the model of Parkinson-like syndrome. The work was performed on 80 male Wistar rats weighing 300-350 g. The injection of thymosin fraction 5 and thymalin to animals corrects clinical traits and behavioral dysfunctions caused by the singular injection of the neurotoxin. It also facilitates conditioned active evasion response in rats, which is especially noticeable at the early stages of memory footprint formation.

Nonclinical studies of biotechnology-derived medicinal products are discussed in the article in terms of new original fusion protein RPH-104 - high potency IL-1β signal pathway antagonist. Specificity of biotherapeutics is connected to complexity of molecules. Efficacy, pharmacokinetic and toxicity nonclinical studies of the biotherapeutics are conducted using relevant species taking into consideration potent immunogenicity. Cytotoxic reactions risk assessment is also important. Accurate nonclinical studies planning can help to obtain sufficient information about potential target organs for toxicity, reversibility of toxic effects and determine safety parameters. According to ethical principles in vivo studies can be optimized using modern in silico analysis, computer modelling and in vitro testing.