Multiple-Dose Safety Study of Ibuprofen/Codeine and Aspirin/Codeine Combinations

¹ The Upjohn Company, Kalamazoo, Ml 49001.

This multiple-dose, double-blind, placebo-controlled, randomized, normal volunteer -study compared formulations of ibuprofen/ codeine and aspirin/ codeine for systemic safety. Vital signs, hematologic, biochemical and urinary parameters, side effects, mood and mental alertness, were monitored. The placebo group had less gastrointestinal side effects and more frequent stools than the active treatment groups. There was statistical evidence for greater adverse effects of aspirin/ codeine on mood and mental alertness in comparison to ibuprofen/ codeine and placebo. Ibuprofen/ codeine had a more favorable adverse effect profile than aspirin/ codeine. A mild respiratory and cardiac depressant effect attributable to codeine was evident in all active treatment groups after 7 days of frequent therapy. More work needs to be done to elucidate the factors regulating the development of tolerance to the respiratory and cardiovascular depressant effects of opiates in general, and for codeine in particular