Toxicology studies with a stable intravenous formulation of nitroglycerin

The preclinical toxicologic profile of Nitrostat, a stable parenteral formulation of nitroglycerin, was determined in mice, rats, rabbits and dogs. Single-dose i.v. studies in rodents yielded LD50 values of 17.3 and 18.2 mg kg-1 in male and female mice, and 24.4 and 23.2 mg kg-1 in male and female rats, respectively. Subacute i.v. studies in rats at doses of 2.5, 5.0 and 10.0 mg per kg per day, and in dogs at doses 1.0 and 3.0 mg per kg per day for two weeks, elicited minimal reactions. In rats, suppression of body-weight gain and food consumption occurred among treated and vehicle-control animals. Mild tissue irritation at injection sites was noted in treated and vehicle-control groups. There were no clearly drug-related clinical or pathological findings in dogs. In rabbits, repeated intravenous administration of Nitrostat did not induce significant local venous irritation. The results of these studies indicated that the stabilized parenteral formulation of nitroglycerin did not elicit unusual toxic properties in intravenous infusion studies.