PROFILE OF ANALGESIC INTERACTION BETWEEN ASPIRIN AND D-PROPOXYPHENE OBTAINED BY MEANS OF THE SURFACE OF SYNERGISTIC INTERACTION

The analgesic effects of aspirin [acetyl salicylic acid (ASA)] and d-p ropoxyphene (PROP) administered either separately or in 24 different c ombinations were determined in the pain-induced functional impairment in the rat (PIFIR) model. This allowed the detection of the profile of analgesic interaction of the combinations. Furthermore, we set out to determine the optimal degree of potentiation obtained with a specific combination of the above drugs by means of the surface of synergistic interaction of the combinations. This parameter was calculated from t he total an algesic effect produced by the combination after having su btracted the analgesic effect produced by each drug alone. The ED(50) for ASA and PROP were 210.4 +/- 1.2 and 66.3 +/- 1.2 mg/kg, respective ly. Over the dose ranges used, the analgesic activities of either ASA or PROP tended to be smaller than those of their respective combinatio ns. Furthermore, 10 combinations showed various degrees of potentiatio n (P < 0.01), while the others (14) exhibited additive analgesic effec ts. The combination of ASA (562.3 mg/kg, po) and PROP (31.6 mg/kg, sc) produced the maximum analgesic effect. However, 5 combinations of ASA with PROP (56.2-56.2, 100-56.2, 177.8-56.2, 316.2-56.2, and 177.8-31. 6 mg/kg) produced the highest potentiation effects. The surface of syn ergistic interaction clearly showed which combination of these analges ic drugs produced the highest degree of potentiation in the rat. This study shows that a specific ratio of combination of analgesic drugs ca n produce optimum potentiation of their analgesic effects. (C) 1995 Wi ley-Liss, Inc.