Abstract
Although nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the main types of drugs used to treat pain, they have several adverse effects, and such effects can be reduced by combining two analgesic drugs. The aim of this study was to evaluate the nociceptive activity of methyleugenol combined with either diclofenac or ketorolac, and determine certain parameters of pharmacokinetics. For the isobolographic analysis, the experimental effective dose 30 (ED30) was calculated for the drugs applied individually. With these effective doses, the peak plasma concentration (Cmax) was found and the other parameters of pharmacokinetics were established. Methyleugenol plus diclofenac and methyleugenol plus ketorolac decreased licking behavior in a dose-dependent manner in phase II, with an efficacy of 32.9 ± 9.3 and 39.8 ± 9.6%, respectively. According to the isobolographic analysis, the experimental and theoretical ED30 values were similar for methyleugenol plus diclofenac, suggesting an additive effect, but significantly different for methyleugenol plus ketorolac (3.6 ± 0.5 vs. 7.7 ± 0.6 mg/kg, respectively), indicating a probable synergistic interaction. Regarding pharmacokinetics, the only parameter showing a significant difference was Cmax for the methyleugenol plus diclofenac combination. Even with this difference, the combinations studied may be advantageous for treating inflammatory pain, especially for the combination methyleugenol plus ketorolac.
Highlights
Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage [1]
According to the dose-response curve, methyleugenol reached an efficacy of 38.7 ± 3.9% at 30 mg/kg (Figure 1B) and had an effective dose 30 (ED30) E of
One alternative to reduce such effects is to combine an nonsteroidal anti-inflammatory drugs (NSAIDs) with a prophylactic. Another is the combination of two NSAIDs that act by distinct mechanisms of action
Summary
Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage [1]. It functions as a defense mechanism to safeguard the integrity of the organism against potentially destructive factors. Pain does not provide a beneficial protective effect, but rather becomes a pathological process that requires treatment [2]. Emotional, discriminatory, sensory, affective, and cognitive aspects, which can lead to a low quality of life together with high social and economic costs [3]. Four main types of pain are currently recognized, classified by duration and the physiopathological characteristics: nociceptive, functional, neuropathic, and inflammatory [4].
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