[The pharmacology of the new combined anti-arrhythmia preparation metatsizin]. / K farmakologii novogo kombinirovannogo antiaritmicheskogo preparata metatsizina.

The combined antiarrhythmic effect of ethmosin and ethacisin in various dose ratios was studied in conscious dogs with two-stage ligation of the coronary artery (after Harris). A 6:1 ratio was found to be optimal for manifestation of the antiarrhythmic effect. In such a ratio of the doses the antiarrhythmic effect of a combination of ethmosin and ethacisin is essentially higher than the activity of each component. On the grounds of these data a combined antiarrhythmic drug methacisin was developed. It possesses a broad spectrum of antiarrhythmic activity. The drug is effective on models of arrhythmias specific of class I, III, and IV antiarrhythmics. Metacisin does not change hemodynamics and activity of the heart. Study of metacisin pharmacokinetics showed that it possesses bioavailability twice that of ethmosin tablets taken separately and four times that of ethasicin.

[Anti-arrhythmic effect and kinetic parameters of bonnecor in the treatment of extrasystole in patients with acute myocardial infarction]. / Antiaritmicheskii éffekt i kineticheskie parametry bonnekora pri lechenii ékstrasistolii u bol'nykh ostrym infarktom miokarda.

Bonnecor was tested for its antiarrhythmic activity in patients with acute myocardial infarction in the first 24 hours of the disease complicated by arrhythmias as ventricular premature beats (VPB). Proceeding from the comparison of its clinical efficiency and pharmacokinetic parameters in 38 patients, the optimal dosage of the drug was formulated. When given intravenously to the patients in dose of 25-37.5 mg bonnecor produced 92% antiarrhythmic responses, failed to shorten heart rate and to lower blood pressure; the agent led to a prolonged P-Q interval as evidenced by ECG. The antiarrhythmic activity, the dose of the drug, and its plasma concentration were found to be closely related. The mean effective bonnecor concentration was ascertained to be 0.45 +/- 0.24 micrograms/ml.

[The pharmacodynamics and pharmacokinetics of bonnecor in patients with different disorders of the heart rhythm]. / Farmakodinamika i farmakokinetika bonnekora u bol'nykh s razlichnymi narusheniiami ritma serdtsa.

The clinical pharmacokinetics and the effect of bonnecor on parameters of the pharmacodynamics were studied in 53 patients with cardiac rhythm disorders, including 23 patients in the acute period of myocardial infarction. At intravenous administration of bonnecor in a dose of 0.4-0.6 mg/kg there was noted a pronounced antiarrhythmic effect with respect to both ventricular and supraventricular cardiac rhythm disorders. Bonnecor exerted no significant effect on the hemodynamic parameters. The pharmacokinetic parameters of bonnecor possess a great variability, the mean values of the parameters are close to the corresponding ones for ethacizine. Along with the unchanged drug one can detect in the blood mono-N-demethylated metabolite. The ranges of effective concentrations and those inducing side effects of the drug are given.

Ethacizin metabolism in humans.

1. The major metabolites of ethacizin (ethyl 10-[3-diethylaminopropionyl]phenothiazine-2-carbamate) have been isolated from human urine by h.p.l.c. and identified by determination of u.v., i.r., n.m.r. and mass spectra and comparison with spectra of synthetic standard compounds. 2. The pathways of metabolism of ethacizin include N-de-ethylation, sulphoxidation, N-10 amide hydrolysis, aromatic hydroxylation and conjugation.

[Clinical pharmacokinetics and hemodynamics of ethacizin in the acute period of myocardial infarct]. / Klinicheskaia farmakokinetika i gemodinamika étatsizina v ostrom periode infarkta miokarda.

Clinical pharmacokinetics of ethacizine and its effect on parameters of the central and peripheral hemodynamics in the acute period of myocardial infarction were studied. The appearance of an additional maximum or "concentration plateau" on the concentration-time curve following a single intravenous injection of the drug was noted in most cases. To describe experimental data, a three-compartment model with lag time was proposed. The pharmacokinetic parameters obtained indicate that ethacizine is characterized by a less value of clearance and greater period of half-elimination as compared to ethmozine. Ethacizine was shown to exert no considerable effect on hemodynamics that makes it possible to recommend its use in acute myocardial infarction when cardiac rhythm disorders occur.

[Pharmacodynamics and pharmacokinetics of disopyramide phosphate]. / Farmakodinamika i farmakokinetika dizopiramida fosfata.

Based on pharmacodynamic and pharmacokinetic studies in 42 patients with paroxysmal and extrasystolic abnormalities of the rhythm it was established that disopyramide phosphate (ritmilen) is an effective antiarrhythmic agent for atrial fibrillation paroxysms. The drug exerts negative, chronotropic, dromotropic and inotropic effects, especially upon intravenous injections for removal of atrial fibrillatin paroxysms. Ritmilen moderately reduces the blood pressure. When used for removal of atrial fibrillation paroxysms ritmilen is effective in doses of 1.2-1.7 mg/kg intravenously and in doses of 2.5-3.8 mg/kg per os. In patients with chronic ventricular premature heart beat the single effective drug doses amount to 0.61-1.7 mg/kg. After oral use the ritmilen concentration in blood plasma is lower than after intravenous use in adequate doses. No relationship has been found between the drug antiarrhythmic effect and blood plasma concentration.