Electrocardiographic and Cardiovascular Changes in Cats and Dogs Caused by High Doses of Amitriptyline Given as Conventional Tablets or a Sustained Release Preparation

Abstract

Electrocardiographic and hemodynamic changes were compared in anesthetized cats and in conscious dogs after high doses of amitriptyline [a tricyclic antidepressant drug] given as conventional tablets or as a sustained release form. Plasma or serum levels of amitriptyline and nortriptyline were determined. In anesthetized cats, tablets caused marked ECG changes in all 6 animals combined with pronounced acidosis in 3 of the animals. The sustained release form caused no ECG changes in 4 animals and moderate disturbances in 2 animals, without acidosis in any of the 6 cats. Almost identical hemodynamic changes were seen in both groups. The plasma levels did not indicate poorer absorption from one preparation than from the other. In conscious dogs, tablets caused marked clinical signs including restlessness, sedation and convulsions (2 dogs). Pronounced ECG changes were seen in all 4 dogs. Bundle branch block developed in 3 dogs. The sustained release preparation caused slight to moderate sedation and no convulsions. Pronounced ECG changes without bundle branch block were seen in 1 dog. Moderate changes were seen in the remaining dogs. Acidosis was most pronounced after the tablets. The serum drug levels clearly show that the absorption is much slower after administration of the sustained release preparation than after tablet administration, and that somewhat lower amounts of drug are absorbed from the sustained release preparation than from tablets. Administration of high doses of amitryptiline as a sustained release preparation causes less toxic manifestations than given as conventional tablets. Part of the explanation may be that less amitryptyline is absorbed from the sustained release preparation than from tablets because of the high dose (dogs), but the main reason is most likely that the absorption from the sustained release preparation is much slower than the absorption from tablets.