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Supra-Additive Interaction of Docosahexaenoic Acid and Naproxen and Gastric Safety on the Formalin Test in Rats.
- Source :
-
Drug development research [Drug Dev Res] 2017 Nov; Vol. 78 (7), pp. 332-339. Date of Electronic Publication: 2017 Aug 03. - Publication Year :
- 2017
-
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 <subscript>30</subscript> 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 <subscript>0-</subscript> <subscript>t</subscript> 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.<br /> (© 2017 Wiley Periodicals, Inc.)
- Subjects :
- Administration, Oral
Animals
Docosahexaenoic Acids pharmacokinetics
Dose-Response Relationship, Drug
Drug Synergism
Drug Therapy, Combination
Female
Male
Naproxen pharmacokinetics
Pain Measurement drug effects
Rats
Rats, Wistar
Docosahexaenoic Acids administration & dosage
Naproxen administration & dosage
Pain drug therapy
Stomach drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1098-2299
- Volume :
- 78
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Drug development research
- Publication Type :
- Academic Journal
- Accession number :
- 28771757
- Full Text :
- https://doi.org/10.1002/ddr.21396