Role of vitamin-E on rat liver-amiodarone: an ultrastructural study

Amiodarone, a class III antiarrhythmic drug, has been found to be effective in the management of patients with life-threatening ventricular arrhythmias. The aim of this study was to test whether the co administration of vitamin-E with amiodarone can reduce amiodarone-induced liver damage. Twelve male albino rats were divided into three groups [ml vegetable oil/day by oral gavages daily for 2 weeks and were used as control group. The rats of the second group received 5.4 mg amiodarone/100 gm rat dissolved in vegetable oil daily by oral gavages for 2 weeks. In the third group, the rats received 5.4 mg amiodarone and 5 mg vitamin-E/100 gram rat dissolved in 2 ml vegetable oil by oral gavages daily for 2 weeks. Two weeks after treatment, the rats were sacrificed and liver specimens were immediately taken and processed for transmission electron microscopic examinations. Sections from the rat liver receiving amiodarone examined by electron microscopy showed disrupted hepatocytes with increased vacuolations. Degenerated organelles and disrupted nuclei were observed. The microvilli of bile canaliculi were disrupted and the hepatocytes showed increased lipid contents. Both endothelial cells and Kupffer cells were damaged. Phospholipids inside the mitochondria showed a loss of cristae. Sections from the liver of rats received amiodarone and vitamin-E showed lesser effects, especially in depositions of phospholipids in the mitochondria and the whole organelles and the nucleus showed minor damage in comparison to the previous group. Milder hepatotoxic effects are seen in rats administered amiodarone and vitamin E simultaneously suggesting that vitamin-E may play a role in amelioration of the effects of amiodarone

Amiodarona en alta dosis de carga oral única: parámetros farmacocinéticos en pacientes sometidos a cirugía coronaria / High loading dose of amiodarone: pharmacokinetics in patients undergoing coronary

Antecedentes: Amiodarona (A) es la droga antiarrítmica más utilizada en la actualidad. No obstante, algunos aspectos de su compleja farmacología son todavía poco conocidos en ciertos grupos de pacientes. Objetivo: Estudiar los parámetros farmacocinéticos de A después de una alta dosis de carga oral en pacientes (P) sometidos a cirugía coronaria. Métodos: Cuarenta y tres P sometidos a cirugía coronaria recibieron una dosis oral de 30 mg/kg en dosis fraccionada como tratamiento profiláctico de arritmias en el post operatorio. Las concentraciones sanguíneas de la droga fueron medidas a tiempos sucesivos, por HPLC, hasta las 96 h de su administración. En base a la curva obtenida de concentración sanguínea vs tiempo, los parámetros farmacocinéticos fueron calculados mediante un programa computacional independiente del modelo compartimental. Resultados: La concentración sanguínea de A alcanzó un valor máximo de 2,3 +/- 1,5µg/ml a las 10 h de la administración de la droga. Posteriormente, se observó un descenso gradual con un valor de 0,4 +/- 0,1 µg/ml a las 96h de administración. Los parámetros farmacocinéticos obtenidos fueron: Vida media 29,1 +/- 11,3h; Area bajo la curva 0’96 63,6 +/- 22,3 (µg/ml)h; Clearance total 6,1 +/- 2,2 ml/min/kg; Volumen de distribución 15,6 +/- 5,4 L/kg. Conclusiones: La farmacocinética de A presenta diferencias con lo encontrado en estudios de dosis única en otros grupos de pacientes. El presente trabajo puede servir para esquemas de dosificación menos empíricos de A.

Background: Amiodarone is currently the most commonly used antiarrhythmic drug. However, some aspects of its complex pharmacokinetics in particular groups of patients are not well known. Aim: to study the pharmacokinetics of amiodarone after a high loading oral dose in patients undergoing coronary revascularization surgery. Methods: Forty three patients operated on for coronary artery disease received oral dose amiodarone, 30mg/Kg, in a fractioned dose as a prophylactic antiarrhythmic medication following surgery. Blood amiodarone concentration was measured at successive intervals for 96 hr. A software based on a non compartmental model was used to determine pharmacokinetic parameters. Results: Maximal blood concentration of amiodarone was 2.3 +/-1.5µg/ml 10hr after drug administration. A subsequent gradual decrease of amiodarone blood level was observed, down to 0.4 +/- 0.1µg/ml at 96hr post drug administration. The half-life time was 29.1 +/- 11.3hr. The area under de 0 to 96hr curve was 63.6 +/- 22.3µg/ml.Total clearance was 6.1 +/- 2.2 ml/min/kg. The distribution volume was 15.6 +/- 5,4 L/kg. Conclusion: Pharmacokinetics of amiodarone differs from that obtained following a single dose in other groups of patients. The data provided may be used to determine more objective amiodarone dosing schemes.

Amiodarona intravenosa / Acute intravenous amiodarone administration

En México se utiliza ampliamente la presentación intravenosa de la amiodarona, y aunque de la misma sustancia que la que se administra por vía oral, su fórmula galénica, así como los efectos de plasticidad celular que esta sustancia tiene sobre el miocardio cuando se administra crónicamente, hacen que estas dos formas de administración se comporten como si se tratara de dos antiarrítmicos diferentes con nombre igual. Se presenta una breve revisión sobre la farmacodinamia de esta sustancia, uno de los antiarrítmicos más indicados en nuestro país

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

Carbamazepine kinetics in cardiac patients before and during amiodarone

Carbamazepina e amiodarona podem frequentemente ser usadas em conjunto, especialmente em países em que as cardiomiopatias säo comuns. Neste estudo doses de carbamazepina (400 mg) foram administradas a pacientes com doenças cardíacas antes e depois de um mês de terapia com amiodarona, 400 mg ao dia. O perfil cinético da carbamazepina, sua fraçäo livre e o nível sérico da amiodarona, foram avaliados nas duas ocasiöes. Näo foram observadas diferenças estatísticamente significantes na cinética da carbamazepina ou mesmo em sua fraçäo livre, antes e depois da introduçäo da amiodarona. A concentraçäo da amiodarona após um mês de terapia foi baixa. Conclui-se que a possível interaçäo no metabolismo hepático näo foi demonstrada devido as baixas concentraçöes de amiodarona, que provavelmente tenham sido suficientes para inibir o metabolismo da carbamazepina

Estudio retrospectivo para el análisis de los efectos colaterales de la amiodarona / Retrospective study of the side effects of amiodarona

Se realizó el análisis retrospectivo de 130 pacientes, tratdos con amiodarona, vistos en la Clínica de Arritmias de este Instituto desde marzo de 1981 hasta mayo de 1988, con el fin de conocer la frecuencia de los efectos colaterales del fármaco. El grupo estuvo constituído por 67 hombres y 63 mujeres, con edades extremas de 20 meses y 82 años; el tiempo promedio semanal empleado fue de 1.05 g. Todos tuvieron un examen clínico completo, radiológico, ECG y de laboratorio. De ellos, 86 tuvieron además por lo menos un estudio electrofisiológico; a los 118, se les realizaron pruebas periódicas de la función tiroidea. Todos fueron revisados cada 3 a 6 meses. Resultados: la respuesta terapéutica fue buena o excelente en el 83% de los casos. No se observaron cambios electrocardiográficos estadísticamete significativos (duración del PR, QRS, QT). En los exámenes oftalmológicos se documentaron depósitos corneales en el 48% de los pacientes, en ning'n caso fue motivo para la suspensión del tratamiento y en diez se observó regresión espontánea de los depósitos. HUbo alteraciones tiroideas en el 33.8%: 14 tuvieron hipotiroidismo y siete hipertiroidismo, el resto bocio simple; en cuatro casos se descontinuó la medicación por alteraciones tiroideas. Se encontraron lesiones dermatológicas en el 4% de los casos; en ninguno se documentaron datos de toxicidad pulmonar. La respuesta terapéutica fue adecuada en la mayoría de los pacientes; aunque la frecuencia de efectos colaterales fue alta, la suspensión del tratamiento se realizó en un porcentaje reducido