RESUMEN
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.
Asunto(s)
Antiarrítmicos/farmacología , Moricizina/farmacología , Fenotiazinas/farmacología , Aconitina , Animales , Antiarrítmicos/farmacocinética , Antiarrítmicos/uso terapéutico , Arritmias Cardíacas/inducido químicamente , Arritmias Cardíacas/tratamiento farmacológico , Compuestos de Bario , Cloruros , Perros , Combinación de Medicamentos , Evaluación Preclínica de Medicamentos , Electrocardiografía/efectos de los fármacos , Semivida , Frecuencia Cardíaca/efectos de los fármacos , Moricizina/farmacocinética , Moricizina/uso terapéutico , Fenotiazinas/farmacocinética , Fenotiazinas/uso terapéutico , Cloruro de Potasio , Conejos , Ratas , Factores de TiempoRESUMEN
The pharmacokinetics and pharmacodynamics of bonnecor were studied simultaneously in animals with experimental arrhythmia. It was shown that irrespective of the animal species and individual features of the drug elimination kinetics the level of bonnecor concentration correlated with the antiarrhythmic effect. The data on the excretion of bonnecor and its metabolites in the urine in the dog and man were obtained. The decrease of bioavailability at oral administration of bonnecor was demonstrated to be related to its intensive conversion in metabolite M-I.
Asunto(s)
Antiarrítmicos/farmacocinética , Dibenzazepinas/farmacocinética , Animales , Antiarrítmicos/análisis , Antiarrítmicos/farmacología , Antiarrítmicos/uso terapéutico , Disponibilidad Biológica , Complejos Cardíacos Prematuros/tratamiento farmacológico , Complejos Cardíacos Prematuros/metabolismo , Gatos , Dibenzazepinas/análisis , Dibenzazepinas/farmacología , Dibenzazepinas/uso terapéutico , Perros , Evaluación de Medicamentos , Evaluación Preclínica de Medicamentos , Humanos , Taquicardia/tratamiento farmacológico , Taquicardia/metabolismo , Factores de TiempoRESUMEN
Pharmacokinetics and pharmacodynamics of ethacizin were studied in a model of rhythm adoption by the heart, with the drug administered intravenously to anesthetized cats. A relation was demonstrated between blood ethacizin pattern and the drug's biphasic effect on the adoption of stimulation-imposed pace by the heart and ventricular fibrillation threshold. The estimated correlation coefficients, reflecting the relationship between the development of ethacizin anti-arrhythmic and antifibrillation effects and variation of its plasma levels between 10 and 120 min after the administration, were rather high (-0.85 and +0.93, respectively). Ethacizin shows anti-arrhythmic and antifibrillation activity when its plasma levels are between 2400 and 200 ng/ml.