Evaluation of the Toxicokinetic Study of 1,2-Propanediol Dinitrate (PGDN) in the Dog

摘要

Bolus injections of PGDN, an organic dinitrate, were made intravenously to dogs at four (4, 10, 40 and 100 mg/kg) dose levels. Dynamic effects were dose related and both physiological and biochemical in nature. The physiological changes were maximized during the fast distribution phase of PGDN in the central compartment. These included the vasodilation effects of decreased systolic, diastolic and pulse blood pressures. A reflex increase in heart rate ensued which was significantly dose related with a maximum attainable increase of 129.5 beats per minute. One biochemical manifestation of PGDN intoxication was an increase in methemoglobin. Values as high as 50% contributed to a delayed drug effect of increased heart rate. Urine production, presumably changed due to blood pressure, decreased inversely with PGDN dose. An unexpected occurrence associated with this decrease was the appearance of whole blood cells in the urine. Light microscopic histopathology was unable to determine the damage site.