30-Day Continuous Intravenous Infusion of 8-Chloroadenosine-3', 5'-Cyclic Monophosphate (NSC-614491) in Beagle Dogs.

摘要

Continuous intravenous infusion of doses of 0.34, 0.67, and 6.67 mg/kg/hr of 8-chloroadenosine-3 feet, 6 feet -cyclic monophosphate (8-Cl-cAMP) were administered to Beagle dogs for periods of 30 hours to 25 days. All dogs given infusions at 0.67 and 6.67 mg/kg/hr died on study. Both dogs inthe 0.34 mg/kg/hr dose group would have died if their infusions had not been discontinued on day 25. Primary organs of toxicity were the gastrointestinal tract and the kidneys. Effects noted were decreases in food consumption and elevations of BUN, creatinine, and glucose concentrations. Pharmacokinetics of 8-Cl-cAMP were poorly characterized in several dogs due to the failure to achieve drug steady state levels. 8-Cl-cAMP exhibited nonlinear, dose-dependent pharmacokinetics with decreasing total body clearance values, increasing volume of distribution values, and increasing elimination half-life values with the increase in drug delivery rates.