In vivo effects of meloxicam and aspirin on blood, gastric mucosal, and synovial fluid prostanoid synthesis in dogs.
OBJECTIVE
To evaluate in vivo activity in dogs of meloxicam or aspirin, previously shown in vitro to be a selective cyclooxygenase-2 (COX-2) inhibitor (COX-1 sparing drug), or a nonselective COX inhibitor, respectively.


METHODS
12 male dogs with unilateral osteoarthritis of the stifle joint.


METHODS
Each dog was treated in a crossover design with aspirin or meloxicam for 21 days. Prostaglandin E2 (PGE2) concentrations were measured at days 0 (baseline), 7, and 21 of each treatment period in lipopolysaccharide (LPS)-stimulated blood, synovial fluid collected by arthrocentesis, and endoscopic gastric mucosal biopsy specimens. Thromboxane B2 (TXB2) was evaluated in blood on days 0, 7, and 21 of each treatment period.


RESULTS
Aspirin administration significantly suppressed PGE2 concentrations in blood, gastric mucosa, synovial fluid, and suppressed TXB2 concentration in blood at days 7 and 21. Meloxicam administration significantly suppressed PGE2 concentrations in blood and synovial fluid at days 7 and 21, but had no effect on concentrations of TXB2 in blood or PGE2 in gastric mucosa. Suppression of LPS-stimulated PGE2 concentrations in blood and synovial fluid by aspirin and meloxicam administration is consistent with activity against the COX-2 isoenzyme. Suppression of concentrations of PGE2 in the gastric mucosa and TXB2 in blood by aspirin administration is consistent with activity against COX-1. Meloxicam, in contrast, had a minimal effect on functions mediated by COX-1.


CONCLUSIONS
Meloxicam acts in vivo in dogs as a COX-1 sparing drug on target tissues by sparing gastric PGE2 synthesis while retaining antiprostaglandin effects within inflamed joints.
Jones
Christopher J
CJ
Department of Small Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens 30602, USA.
Streppa
Heather K
HK
Harmon
Barry G
BG
Budsberg
Steven C
SC
D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D018592:Cross-Over Studies; D051545:Cyclooxygenase 1; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis / Q000097:blood; D004283:Dog Diseases / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology; D004285:Dogs; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008297:Male; D000077239:Meloxicam; D010003:Osteoarthritis / Q000097:blood / Q000188:drug therapy / Q000201:enzymology / Q000662:veterinary*; D011451:Prostaglandin-Endoperoxide Synthases; D013264:Stifle; D013582:Synovial Fluid / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D013843:Thiazines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000096:biosynthesis / Q000097:blood
D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D013843:Thiazines; D013844:Thiazoles; D013929:Thromboxane B2; D051545:Cyclooxygenase 1; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D001241:Aspirin; D000077239:Meloxicam