TY - JOUR
T1 - Supra-Additive Interaction of Docosahexaenoic Acid and Naproxen and Gastric Safety on the Formalin Test in Rats
AU - Arroyo-Lira, Arlette Guadalupe
AU - Rodríguez-Ramos, Fernando
AU - Ortiz, Mario I.
AU - Castañeda-Hernández, Gilberto
AU - Chávez-Piña, Aracely Evangelina
N1 - Publisher Copyright:
© 2017 Wiley Periodicals, Inc.
PY - 2017/11
Y1 - 2017/11
N2 - (Table presented.). 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 ED30 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 AUC0- t 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.
AB - (Table presented.). 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 ED30 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 AUC0- t 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.
KW - antinociception
KW - docosahexaenoic acid
KW - gastric injury
KW - naproxen
KW - supra-additive interaction
UR - http://www.scopus.com/inward/record.url?scp=85026738087&partnerID=8YFLogxK
U2 - 10.1002/ddr.21396
DO - 10.1002/ddr.21396
M3 - Artículo
SN - 0272-4391
VL - 78
SP - 332
EP - 339
JO - Drug Development Research
JF - Drug Development Research
IS - 7
ER -