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Profile of analgesic interaction between aspirin and d‐propoxyphene obtained by means of the surface of synergistic interaction
Author(s) -
LópezMuñoz Francisco J.
Publication year - 1995
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430350104
Subject(s) - analgesic , propoxyphene , aspirin , salicylic acid , pharmacology , chemistry , long term potentiation , drug interaction , anesthesia , drug , medicine , receptor , biochemistry
Abstract The analgesic effects of aspirin [acetyl salicylic acid (ASA)] and d‐propoxyphene (PROP) administered either separately or in 24 different combinations 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 the total analgesic effect produced by the combination after having subtracted 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, respectively. Over the dose ranges used, the analgesic activities of either ASA or PROP tended to be smaller than those of their respective combinations. Furthermore, 10 combinations showed various degrees of potentiation ( P < 0.01), while the others (14) exhibited additive analgesic effects. 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 synergistic interaction clearly showed which combination of these analgesic drugs produced the highest degree of potentiation in the rat. This study shows that a specific ratio of combination of analgesic drugs can produce optimum potentiation of their analgesic effects. © 1995 Wiley‐Liss, Inc.