No abstract

Preclinical Research The aim of this work was to evaluate the effect of docosahexaenoic acid (DHA) on the pharmacokinetics and pharmacodynamics-nociception-of naproxen in rats, as well as to determine the gastric safety resulting from this combination versus naproxen alone. Female Wistar rats were orally administered DHA, naproxen or the DHA-naproxen mixture at fixed-ratio combination of 1:3. The antinociceptive effect was evaluated using the formalin test. The gastric injury was determined 3 h after naproxen administration. An isobolographic analysis was performed to characterize the antinociceptive interaction between DHA and naproxen. To determine the possibility of pharmacokinetic interactions, the oral bioavailability of naproxen was evaluated in presence and absence of oral DHA. The experimental effective dose ED values (Zexp) were decreased from theoretical additive dose values (Zadd; P < 0.05). The isobolographic analysis showed that the combination exhibited supra-additive interaction. The oral administration of DHA increased the pharmacokinetic parameter AUC of naproxen (P < 0.05). Furthermore, the gastric damage induced by naproxen was abolished when this drug was combined with DHA. These data suggest that oral administration of DHA-naproxen combination induces gastric safety and supra-additive antinociceptive effect in the formalin test so that this combination could be useful to management of inflammatory pain. Drug Dev Res 78 : 332-339, 2017. © 2017 Wiley Periodicals, Inc.

Pain is a multidimensional sensory experience that is intrinsically unpleasant and associated with hurting and soreness, it is essentially a sensation. Pain has strong, cognitive and emotional components, it is linked to, or described in terms of suffering. Nonsteroidal Anti-inflammatory Drugs (NSAIDs) and opioid analgesics are two of the most common types of drugs used for pain management. However, the use of these analgesics is limited by the presence of significant adverse effects. A useful practice is a combination of two agents with the same therapeutic effect wherein each agent is administered to obtain additive, synergistic or subadditive interaction in a fixed ratio. If the combination resulted in addition or synergism, the doses employed by each agent are reduced, then the side effects are absent; this kind of study is named isobolographic analysis. In this review, the authors summarized previous reports of the combination of NSAIDs with opioids and natural products as an alternative in the pain management.