Studies on Acute Toxicity and Drug Levels of Citalopram in the Dog

Abstract

ECG and hemodynamic changes were studied in conscious dogs after a sublethal oral dose (20 mg/kg) of citalopram. The effects of continuous i.v. infusion of citalopram (10 mg/kg per h) were studied in conscious and anesthetized dogs. The findings were related to plasma levels of citalopram. Severe convulsive attacks occurred in conscious dogs after infusion of 21.3 or 26.5 mg/kg and after the oral dose. The convulsions were successfully treated with diazepam. Convulsions were not seen in the anesthetized dogs. They died from respiratory arrest after infusion of 42.2 or 61.3 mg/kg. Atrioventricular and intraventricular conduction was unchanged and ECG changes were negligible. Sinus tachycardia which could be reversed by diazepam and moderate hemodynamic changes were seen. Since no ECG changes were seen in conscious dogs even during pauses in the convulsive seizure, citalopram evidently does not exert cardiotoxic effects in the dog. Good correlation was found between general clinical findings and citalopram levels in plasma. Conscious dogs were exposed to drug levels exceeding those of the average patient by .apprx. 20-fold, while anesthetized dogs had considerably higher concentrations.