Bioequivalencia de una formulación nacional de ambroxol / Bioavailability comparison between a Chilean generic preparation of ambroxol and the original product

Objetivos: Determinar la biodisponibilidad relativa de un jarabe de ambroxol, genérico, comercializado en Chile, respecto a la de mucosolvan de Boehringer Ingelheim, producto innovador. Métodos: estudio aleatorio, cruzado, de doble ciego en 12 voluntarios, hombres sanos, que recibieron una dosis oral única de 90mg de jarabe del fármaco genérico y de mucosolvan con un período de separación de 14 días. La determinación del fármaco se realizó por un método de cromatografía líquida de alta resolución validado. Resultados: los límites de confianza de 95 porciento para todas las variables están dentro de los de bioequivalencia aceptados de 80-125 porciento, no encontrándose diferencias estadísticamente significativas en los parámetros farmacocinéticos promedios utilizados en estos estudios: Cmáx (concentración máxima), ABC0-t(área bajo la curva de concentración plasmática vs tiempo post administración entre 0 y un tiempo determinado) y ABC0-oo (área bajo la curva de concentración plasmática vs tiempo post administración entre 0 e infinito) de cada producto. Tampoco se encontró diferencias para los parámetros: tmáx (tiempo el cual se alcanza la Cmáx), Ka (constante de velocidad de absorción), Ke (constante de velocidad de eliminación), t½(tiempo de vida media de eliminación), y Cl(clearance) encontrados para cada producto. Conclusion: los resultados farmacocinéticos indican que el jarabe genérico es bioequivalente al innovador, pudiéndose intercambiar como mucolíticos

Fibrilación auricular focal: características clínicas y resultado de la ablación con radiofrecuencia / Results of radiofrequency ablation in focal atrial fibrillation

Background: Atrial fibrillation can originate in arrhythmogenic foci coming from the pulmonary veins. Patients with atrial fibrillation, initiated from triggering foci, can be treated with radiofrequency ablation. Aim: To report the results of radiofrequency ablation in patients with focal atrial fibrillation. Patients and methods: Thirteen patients with focal atrial fibrillation (8 male, aged 19 to 60 years old) are reported. Twelve had frequent crises refractory to antiarrhythmic drugs. Two had also flutter and tachycardia. One had a permanent atrial fibrillation lasting five years. Two had ventricular dysfunction and left atrial dilatation. The triggering focus was identified during the electrophysiological study, by the precocity of the potential that initiated the atrial fibrillation. Results: All patients had early atrial extrasystolic beats, isolated or repetitives, that preceded atrial fibrillation. During the electrophysiological study, 18 foci (3 in the right and 15 in the left atrium all in pulmonary veins) were identified. Radiofrequency ablation had immediate success in 11 patients. In 5, a flutter was also ablated. One patient had a sinus dysfunction after the procedure and atrial fibrillation was not eliminated. In this and other patient in whom the procedure failed, a pacemaker was implanted and the atrioventricular node was blocked. In a follow up, ranging from 4 to 31 months, eight patients are asymptomatic and 3 recidivated. No complications have been detected. Conclusions: Patients with focal atrial fibrillation have common clinical and electrocardiographic features. Radiofrequency ablation of the triggering focus is possible and effective in most cases

Desfibrilador implantable en el manejo de taquiarritmias ventriculares malignas: experiencia del Centro Nacional de Arritmias / Implantable defibrillators in the management of malignant ventricular tachyarrhythmias

Background: Implantable defibrillators are the most effective means to prevent sudden death in patients with malignant ventricular tachyarrhythmias. The availability of this type of devices is limited in Chile, due to their high price. Aim: To report the first patients treated with implantable defibrillators in our hospital. Patients and methods: Nine males and one female aged 13 to 65 years old are reported. Three presented with ventricular fibrillation (presenting out of the hospital in three) and the rest had ventricular tachycardia resistant to drugs or radiofrequency ablation. Results: All implantswere performed using intracardiac electrodes. The generator was implanted in the pectoral region in nine and in the abdomen in one. A successful defibrillation was obtained with less than 15 J in four patients, with 20 J in three and with 24 J in three. There were no complications during the procedure. After a 12 months follow up, four patients have been treated by the implantable device. One of these subjects had a ventricular fibrillation in two occasions. One patient died of a bronchopneumonia two years after the implant. Conclusions: Implantable defibrillators are an effective therapy for the treatment of malignant ventricular arrhythmias with a high risk of sudden death

Muerte súbita por fibrilación ventricular recuperada: ¿síndrome de Brugada? / Sudden death due to ventricular fibrillation: a case of Brugada syndrome?

We report a 47 years old male who was recuperated from a sudden death, and in whom the cardiological assessment showed a right bundle branch block and a fluctuating ST segment elevation from V1 to V3. During the electrophysiological study, a polymorphic tachycardia and a ventricular fibrillation were induced. Procainamide administration enhanced ST segment alterations in right precordial leads, and isoproterenol normalized the EKG. All these disturbances are similar to the condition described by Brugada brothers. The patient was treated with an internal implantable defibrillator, without the use of antiarrhythmic drugs and is well after four months of follow up

Concentraciones plasmáticas y relación amiodarona/desetilamiodarona en pacientes sometidos a tratamiento crónico / Serum concentrations and amiodarone/desethylamiodarone relation in patients receiving chronic treatment

We measured plasma concentrations of amiodarone and desethylamiodarone by HPLC in 44 outpatients aged 24 to 67 years old (21 male), receiving the drug during at least three months. The drug was indicated for supraventricular arrythmias in 37 patients and ventricular arrhytmias in seven. Plasma concentrations of amiodarone, desethylamiodarone and their ratio were 1.71ñ0.82, 0.85ñ0.42 µg/ml and 2.02 respectively, for a mean daily dose of 223ñ88 mg. In 41 patients, arrhytmias were succesfully treated. These patients received a mean daily dose of 220ñ86 mg and concentrations of amiodarone, desethylamiodarone and their ratio were 1.75ñ0.86, 088ñ0.45 µg/ml and 1.99 respectively. In 3 patients with treatment failure, receiving a daily dose of 257ñ115 mg, these figures were 1.2ñ0.3, 0.5ñ0.1 µg/ml and 2.4 respectively. We conclude that our patients had lower plasma concentrations of desethylamiodarone and higher amiodarone/desethylamiodarone ratios than those reported in other countries

Absorción y eliminación de amiodarona después de su administración oral e intravenosa en individuos sanos / Amiodarone absorption and disposal after intravenous administration in healthy individuals

We studied amiodarone absorption and disposal in 8 male helathy subjects aged 21ñ1 years old and weighting 69.8ñ7.1 kg. An intravenous dose of 5 mg/kg and an oral dose of 600 mg of amiodarone were administrated. Amiodarone concentrations were measured by HPLC and calculations were performed using a compartment model independent pharmacokinetic analysis program. After oral administration a Cmax of 1.17ñ0.3 mg/ml was achieved at 3.25ñ0.46 h (tmax). Absolute bioavailability ranged from 50.4 to 87.8 percent (68.6ñ12.6 percent). Compared to previous reports, the variability of this parameter is similar and the mean value is one of the highest informed. After intravenous administration, amiodarone had a half life of 7.35ñ0.96 h, a total body clearence of 4.25ñ0.73 ml/kg/min and a distribution volume of 2.99ñ0.71 l/kg. Except the later figure, which is in the inferior range, all other parameters are within previously reported values. It is concluded that amiodarone absorption and disposal values found in chilean subjects are similar to those reported abroad

Inmunoensayoenzimático homogéneo para la determinación de digoxina plasmática: experiencia clínica y correlación con el radioinmunoensayo / Homogeneus enzimatic immune-assay (H.E.I.A.) for determination of blood levels of digoxin: clinical experience and comparison with radioinmune - assay (RIA)

En el presente trabajo presentamos nuestra experiencia clínica con la determinación de niveles plasmáticos (NP) de Digoxina utilizando el método de Inmunoensayo enzimático homogéneo, EMIT, en muestras de plasma de 50 pacientes hospitalizados en el Hospital Clínico de la Universidad de Chile. El método EMIT se ha señalado como uno de utilidad similar al Radioinmunoensayo (RIA) para Digoxina pero no encontramos información en la literatura que fundamente esta aseveración. En 47 pacientes con función renal normal y sin evidencias de toxicidad el NP encontrado fue de 1,6 ñ 0,5 ng/ml (X ñ DS) con una dosis de 0,23 ñ 0,04 mg/día. Sólo un paciente presentó signos de intoxicación digitálica con un NP de 2,8 ng/ml. Los otros dos pacientes tenían alterada su función renal y presentaron NP de 1,0 y 1,3 ng/ml con dosis de 0,12 mg/día en cada caso. Estos valores son similares a aquellos descritos por la literatura científica en los cuales se utilizó el RIA en la determinación. Utilizando el plasma de doce de los pacientes, se realizó un estudio de correlación midiendo las concentraciones de la droga por ambas técnicas, encontrándose un índice de correlación r = 0,91 (p <0,05). Nuestros resultados aportan evidencias de que el método EMIT es de similar utilidad al RIA con las ventajas de ser más rápido, simple en su ejecución y con un menor costo de instalación