Preclinical Continuous Intravenous Infusion Toxicity Study of Flavone Acetic Acid (NSC-347512) in Beagle Dogs

摘要

The toxicity of flavone acetic acid (FAA, NSC-347512) following continuous i.v. infusion to beagle dogs was determined in a two-phase study. In the preliminary phase, two dogs received FAA at a rate of 70 mg/kg/hr or 35 mg/kg/hr while a third dog served as a vehicle control. Although infusion was intended to continue for 120 hr, severe toxicity limited infusion to 28 hr and 56 hr at the high and low doses, respectively. In the toxicity phase, two groups of dogs (one male and one female each), received three weekly 8-hr infusions of FAA at a rate of 125 mg/kg/hr or 62.5 mg/kg/hr while a third group (one male and one female) served as vehicle controls. During continuous infusion, the steady state plasma levels of FAA were achieved in 8 to 16 hr. The steady state plasma concentrations (Cpss) were 432 and 173 microgram/mL following the high and low doses, respectively. Weekly 8-hr infusions with FAA resulted in maximum plasma concentrations (Cmax) of 239 to 696 microgram/mL following the high dose and 126 to 300 microgram/mL following the low dose.