CLINICAL-PATHOGENETICAL ROLE OF DYNAMICS OF CONCENTRATION OF INTERLEUKIN-6 DEPENDING ON POLYMORPHISM OF ITS GENE IN CONDUCTING ANTIVIRAL THERAPY IN PATIENTS WITH CHRONIC HEPATITIS C.

The study included 83 patients with CHC who received antiviral therapy according to the EASL 2016 recommendations on a 12-week peg-IFN+SOF+RBV schedule. The aim of the study was to determine the role of IL-6 concentration dynamics in relation to the polymorphism of the gene that encodes it, in achieving a SVR during therapy. Based on the results of the study, it was established that the polymorphism of the IL-6 gene (rs1800795) in patients with CHC influenced the dynamics of IL-6 concentration and the effectiveness of AVT.

[Sublingual nitroglycerin: the pharmacokinetic changes following long-term treatment with trinitrolong and nitroderm-TTS].

The effect of the long-term use of prolonged medicinal forms containing nitroglycerin (NG)--trinitrolong and nitroderm-TTS on the pharmacokinetics of sublingual NG was studied. A significant change of the pharmacokinetic parameters at the sublingual use of NG both after the long-term treatment with trinitrolong and after therapy with nitroderm was observed: in both cases the time of half-release of NG from plasma and the average time of retention increased, the area under the curve of concentration-time significantly increased and the drug clearance decreased (for trinitrolong the difference in the clearance parameter is significant). While combining the data on both drugs the difference in the last two parameters also becomes significant.

[An analysis of the concentration-effect relation of glyceryl trinitrate in patients with stenocardia of effort after its single use in prolonged-release drug forms].

There is a correlation between the plasma concentrations of glycerol trinitrate and the antianginal effects of trinitrolong (application on the gingival mucosa) and nitroderm-TTS (application on the skin) in patients with angina pectoris by Hill's formula. The lower limit on the gingival mucosa) and nitroderm-TTS is 0.5-0.

[Nifedipine pharmacokinetics in patients with exertion-induced stenocardia after its single and long-term administration].

A study of the causes of tolerance to antianginal effect of nifedipine++, conducted in 12 patients with angina of effort, examined serum pharmacokinetics of nifedipine++ and its primary metabolite (puridine analogue of nifedipine++), after a single 20 or 30 mg dose and at the end of a treatment course (20-40 mg 3-4 times daily for 2 to 6 months). In addition, the effect of nifedipin treatment on nonspecific microsomal hepatic oxidase activity was assessed by means of the antipyrin test. Pharmacokinetics of both unchanged nifedipin and its primary metabolite showed no change through the nifedipin course, suggesting that tolerance to the antianginal effect of nifedipin may be based on altered systemic pharmacologic response rather than altered pharmacokinetics of nifedipin.

[Methodological approaches to the evaluation of the effectiveness of anti-anginal preparations in patients with stenocardia by 24-hour ECG monitoring].

Scientific rationale are given for methodological approaches promoting improved reproducibility of 24-hour ECG monitoring data, for the method to be used repeatedly in assessing patient's condition. Repeated 24-hour-ECG monitoring in identical motor conditions (a standard mobility regimen) has been shown to improve considerably the reproducibility of its results. Criteria for the efficiency of antianginal therapy in patients with angina of the 2nd and 3d functional classes, as evidenced by 24-hour ECG monitoring, have been developed and substantiated.

[Relation of the anti-anginal effect of nitroglycerin and its blood level in patients with stable exertion-induced stenocardia].

In 8 patients with coronary heart disease and stable angina pectoris of effort, a relationship was examined between nitroglycerin antianginal effects and blood concentration when it was topically applied to the gum (trinitrolong, TNL) and to the skin (nitroderm, ND). A close correlation was found between the antianginal effects and blood concentration (r = 0.97 for TNL and r = 0.

[Study of anti-ischemic effects of verapamil and nifedipine after long-term treatment of patients with exertion-induced stenocardia].

The effects of verapamil and nifedipine taken as single doses and regular treatment, its mean duration being 2.9 and 2.8 months, respectively, were compared by means of repeated standard treadmill exercise in 22 patients with stable angina of effort.

[Pharmacokinetics of verapamil and its N-dealkylated metabolites in patients with chronic ischemic heart disease undergoing long-term monotherapy].

Pharmacokinetics of verapamil (VP) and its main N-dealkylated metabolites (nor-VP, D-617 and D-620) was studied in 10 patients with chronic ischemic heart disease after administration of the first and last doses of the course of treatment (80-120 mg of VP 3-4 times per day for 4-7 months). The antipyrine test was used in 8 patients simultaneously with the study of pharmacokinetics of VP and its metabolites. At the end of the course a decrease of oral clearance of VP as compared with its beginning (from 3.

[Pharmacokinetics of glycerin trinitrate (nitroglycerin) after sublingual administration in patients with chronic ischemic heart disease].

Pharmacokinetics of nitroglycerin was studied in 22 patients with ischemic heart disease associated with angina of effort after sublingual intake of 0.5 mg standard granules. The maximal blood plasma concentration of the drug was shown to occur on the average in 4.

[Comparison of the verapamil concentration of human blood serum and saliva].

Verapamil concentrations were measured in the samples of blood serum and saliva taken at the same time in patients with angina of effort within 0.5-24 hr after administration of a single dose of the drug (14 persons) or the last dose of the course (10 persons). A mean ratio of saliva verapamil concentration to blood serum concentration was 0.

The effect of oral verapamil therapy on antipyrine clearance.

The influence of chronic verapamil treatment on antipyrine elimination was studied in eight angina patients. Antipyrine half-life (mean +/- s.d.

[New approaches to pharmacodynamic research on anti-angina agents].

Methods of evaluating efficacy of antianginal drugs with exercise tests are described. The use of the methods makes it possible to choose adequate antianginal therapy for most patients with ischemic heart disease and stable effort angina and also to control efficacy of treatment with the chosen drug at its regular administration.

[Dynamics of the anti-anginal effect and of the concentrations of verapamil and its metabolites in the blood serum of patients with stenocardia of exertion].

Anti-anginal effect of verapamil was examined in 17 patients with angina of effort (a 120 mg single dose in 10 patients and a 200 mg dose in 7), using repeated identical treadmill exercise with ECG monitoring. Serum levels of verapamil and its three primary metabolites were measured simultaneously. A correlation was demonstrated between verapamil's anti-ischemic effect and serum concentrations, while no significant contribution of the metabolites to the effect could be shown.

[Pharmacokinetics of nifedipine and its metabolite after a single oral dose of the drug in patients with stenocardia of effort].

The pharmacokinetics of nifedipine and its primary metabolite 2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridine carboxylate was studied in 7 patients with angina of effort after a single oral administration of nifedipine ("Corinfar" tablets) in doses of 20 and 30 mg. The binding of nifedipine and its metabolite to blood serum proteins was determined. Nifedipine appeared in the blood serum of the patients 1.

Disposition kinetics and urinary excretion of verapamil and some of its primary metabolites after oral administration in patients with angina pectoris.

Pharmacokinetics of verapamil and of its three primary metabolites [norverapamil, 2-(3,4-dimethoxyphenyl)-2-isopropyl-6-azaheptanitrile (D-617) and 2-(3,4-dimethoxyphenyl)-2-propylamino-3-methylbutyronitrile (D-260)] was studied after oral administration in 7 patients with stable angina pectoris. Serum levels of metabolites were found to be in the same range as that of the intact drug. Areas under the serum concentration time curves of each metabolite were higher and serum half-lives were significantly longer than those of verapamil.

[Dinitrosorbilong--a new Soviet anti-angina preparation. Its comparative pharmacodynamic, pharmacokinetic and clinical study].

The efficacy of dinitrosorbilong (DNL)--a new long-acting isosorbid dinitrate (IDN) preparation applied to the gum--was evaluated in 72 coronary patients with stable angina of effort. Repeated treadmill tests revealed antianginal effect of DNL exceeding 8 hours. The degree and duration of DNL action significantly surpassed those of conventional oral IDN tablets and of some other long-acting IDN preparations.

[Clinico-pharmacological study of a new Russian anti-angina preparation dinitrosorbilong].

Eighty patients with ischemic heart disease and stable angina pectoris of effort were examined for the efficacy of dinitrosorbilong (DNL), a new long-acting drug based on isosorbide dinitrate (ID). The anti-ischemic effect of DNL appraised with the aid of repeated exercise lasted about 8h, which was on the average 4 h longer as compared with the duration of the anti-ischemic effect of ID tablets. The regular intake of DNL favoured an appreciable decrease in the number of angina pectoris attacks making it possible to lower nitroglycerin consumption.

[Cooperative study on the long-term use of anti-anginal preparations (methodologic questions)].

The development of a national collaborative program for the study of long-term effects of antianginal drugs initiated for the first time in our country is reported. The present communication is concerned with methodological approaches to the study. The collaborative effort has enabled a basically new scale of research.

[Comparative clinical study of the effectiveness of the new anti-arrhythmia agents, trimecaine and pyrromecaine].

The antiarrythmic effects of trimecain and pyromecain were studied in 53 patients with frequent ventricular premature beats. Trimecain was given to 22 patients and pyromecain was given to 31. The efficiency of both intravenous and oral drug administration was considered.

[Pharmacokinetic characteristics of trimecaine compared to lidocaine in myocardial infarct patients].

The authors studied pharmacokinetics of trimecain and lidocain in 10 and 15 patients with myocardial infarction, respectively, after a single intravenous jet injection in the dose of 80 mg. The groups were comparable as to age, mass and surface of the body. In all patients the dependence of trimecain and lidocain concentrations on time was biexponential.

[Prevention of ventricular fibrillation using lidocaine in the acute period of a myocardial infarct].

Two randomized investigations have shown a possibility to prevent primary ventricular fibrillation in acute myocardial infarction by lidocain. The first investigation was conducted in an intensive care unit on 316 patients hospitalized on an average 6 hours after the onset of acute myocardial infarction. 155 patients were included into a control group.

[Comparative clinical study of trimecaine and lidocaine as anti-arrhythmia agents in myocardial infarct].

The article discusses the comparative antiarrhythmic effectiveness of trimecaine and lidocaine in patients with acute myocardial infarction in the first 24 hours of the disease. The 45 patients included in the study were separated into 3 groups: the 1st (control) group consisted of 15 patients with acute myocardial infarction who were not given antiarrhythmic or arrhythmogenic agents; the 2nd group was formed of 15 patients who from the time of admission were given trimecaine by intravenous drip at a rate of 2 mg/min for purposes of prevention after preliminary jet-injection of 80 mg of the drug; the 3rd group consisted of 15 patients given lidocaine by the same schedule. An antiarrhythmic effect was noted in 60% of group 2 patients and in 87% of group 3 patients.

[Lidocaine pharmacokinetics when administered intramuscularly].

The pharmacokinetics of lidocain injected intramuscularly in doses of 300-600 mg was studied and compared to that on its intravenous administration in a dose of 80 mg in the same patients with acute myocardial infarction. When injected intramuscularly the drug rapidly and safely reached the systemic circulation. The relationship between the lidocain plasma concentration and time could be depicted adequately by an open one-compartmental model to determine the parameters of the model.

[Sudden death in myocardial infarct, its precursors and the problems of prevention].

Continuous magnetic tape recording of the ECG made it possible to reveal ventricular extrasystoles in 99% of patients with uncomplicated myocardial infarction and extrasystoles, regarded as the precursors of ventricular fibrillation, in 95%. Treatment with lipocaine or trimecaine (103 persons) reduced the frequency of the development of complex gradation of ventricular extrasystoles as compared to a random control group (106 persons). A considerable decrease was also noted in the number of cases with primary ventricular fibrillation in the group of patients treated with antiarrhythmic drugs.