DETERMINATION OF ANALGESIC INTERACTION BETWEEN ACETAMINOPHEN AND D-PROPOXYPHENE OBTAINED BY MEANS OF THE SURFACE OF SYNERGISTIC INTERACTION

The analgesic effects of acetaminophen, p.o., (ACE) and d-propoxyphene , s.c., (PROP) administered either separately or in 24 different combi nations were determined in a model of pain-induced functional impairme nt in the rat This allowed us to detect the analgesic interaction prof ile of the combinations. Furthermore, we set out to determine the opti mal degree of enhancement enhancement obtained with a specific combina tion of the above drugs by means of the surface of synergistic interac tion (SSI) of the combinations. This parameter was calculated from the total analgesic effect produced by the combination after having subtr acted the analgesic effect produced by each drug alone. The ED(50)s fo r ACE and PROP were 286.1 +/- 1.4 mg/kg and 66.3 +/- 1.2 mg/kg, respec tively. Over the dose ranges used, the analgesic activities of both AC E and PROP tended to be smaller than those of their respective combina tions. Furthermore, 11 combinations showed various degrees of enhancem ent (p < 0.01), while the others (13) exhibited additive analgesic eff ects. The combination of ACE (562.3 mg/kg) and PROP (56.2 mg/kg) produ ced the maximum analgesic effect. However 5 combinations of ACE with P ROP (177.8-56.2, 316.2-10.0, 3162-17.8 316.2-56.2 and 562.3-10.0 mg/kg ) produced the highest enhancement. The SSI clearly showed which combi nation of these analgesic drugs produced the highest degree of enhance ment in the rat. This study shows that a specific combination ratio of analgesic drugs can produce optimum enhancement of their analgesic ef fects.