Acute toxicity of propoxyphene salts

Abstract

The acute toxicity of oral and parenteral doses of propoxyphene HCl was studied in laboratory animals. Large iv, im, or ip doses of propoxyphene HCl produced clonic and tonic convulsions in mice, rats, and dogs. Death from oral doses of propoxyphene HCl was preceded by convulsions in dogs but not in rodents or rabbits. Other effects included hypoactivity and body rigidity in rodents, and salivation, ataxia, and weakness in dogs. Animals given lethal doses of propoxyphene showed profound respiratory depression, which was judged to be the primary cause of death. Respective LD50 values for propoxyphene HCl in the mouse, rat, and dog were 28, 15, and 29 mg/kg iv and 282, 230, and 100 mg/kg po. Comparative acute oral toxicity tests were conducted on the 2-naphthalene sulfonate (napsylate) salt of propoxyphene. In equimolar doses, propoxyphene napsylate, a relatively insoluble salt, was about one-half as toxic as propoxyphene HCl in rodents and clearly less toxic in dogs. Plasma concentrations of propoxyphene indicated that the differences in the acute oral toxicity of propoxyphene HCl and propoxyphene napsylate were due to the more gradual absorption of the latter salt.