Supra‐Additive Interaction of Docosahexaenoic Acid and Naproxen and Gastric Safety on the Formalin Test in Rats

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 ra...

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Bibliographic Details
Published in:Drug development research 2017-11, Vol.78 (7), p.332-339
Main Authors: Arroyo‐Lira, Arlette Guadalupe, Rodríguez‐Ramos, Fernando, Ortiz, Mario I., Castañeda‐Hernández, Gilberto, Chávez‐Piña, Aracely Evangelina
Format: Article
Language:English
Subjects:
Administration, Oral
Animals
antinociception
Bioavailability
Docosahexaenoic acid
Docosahexaenoic Acids - administration & dosage
Docosahexaenoic Acids - pharmacokinetics
Dose-Response Relationship, Drug
Drug dosages
Drug Synergism
Drug Therapy, Combination
Female
Formaldehyde
gastric injury
Inflammation
Injury analysis
Male
Naproxen
Naproxen - administration & dosage
Naproxen - pharmacokinetics
Oral administration
Pain
Pain - drug therapy
Pain Measurement - drug effects
Pain perception
Pharmacodynamics
Pharmacokinetics
Pharmacology
Rats
Rats, Wistar
Rodents
Safety
Stomach - drug effects
supra‐additive interaction
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Summary: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 ED30 values (Zexp) were decreased from theoretical additive dose values (Zadd; P 
ISSN:0272-4391
1098-2299
DOI:10.1002/ddr.21396