Document Detail


Effects of firocoxib, meloxicam, and tepoxalin on prostanoid and leukotriene production by duodenal mucosa and other tissues of osteoarthritic dogs.
MedLine Citation:
PMID:  18764695     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To evaluate the in vivo effects of firocoxib, meloxicam, and tepoxalin on prostaglandin (PG) and leukotriene production in duodenal mucosa and other target tissues in dogs with chronic osteoarthritis (OA).
ANIMALS: 8 dogs with chronic, unilateral OA of the stifle joint.
PROCEDURES: In a crossover design, each dog received placebo (no treatment), firocoxib, meloxicam, or tepoxalin for 7 days, followed by a 21-day washout period. On the first day of treatment (day 0; baseline) and days 2, 4, and 7, samples of whole blood, synovial fluid, and gastric and duodenal mucosae were collected. Prostaglandin E2 concentrations were measured in synovial fluid of the stifle joint and after ex vivo stimulation of whole blood samples. Synthesis of PGE1 and PGE2 was measured in samples of gastric and duodenal mucosae. Concentrations of thromboxane B2 (TxB2) were measured in whole blood samples. Leukotriene B4 (LTB4) concentrations were measured in samples of whole blood (ex vivo stimulation) and gastric and duodenal mucosae.
RESULTS: Firocoxib, meloxicam, and tepoxalin significantly suppressed whole blood concentrations of PGE2, compared with baseline and placebo concentrations, at days 2, 4, and 7. Tepoxalin significantly suppressed serum TxB2 concentrations, compared with baseline, firocoxib, meloxicam, and placebo, at all 3 time points. Production of PGE1 and PGE2 was significantly lower in duodenal versus gastric mucosa. Tepoxalin significantly decreased rates of PGE1 and PGE2 in duodenal and gastric mucosae, compared with baseline rates.
CONCLUSIONS AND CLINICAL RELEVANCE: PG production was lower in the duodenum than in the stomach. Firocoxib had a COX-1-sparing effect in vivo.
Authors:
John P Punke; Abbie L Speas; Lisa R Reynolds; Steven C Budsberg
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of veterinary research     Volume:  69     ISSN:  0002-9645     ISO Abbreviation:  Am. J. Vet. Res.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-09-03     Completed Date:  2008-12-19     Revised Date:  2012-10-26    
Medline Journal Info:
Nlm Unique ID:  0375011     Medline TA:  Am J Vet Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1203-9     Citation Subset:  IM    
Affiliation:
Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
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MeSH Terms
Descriptor/Qualifier:
4-Butyrolactone / analogs & derivatives,  pharmacology
Animals
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
Dog Diseases / drug therapy*
Dogs
Duodenum / drug effects*
Female
Intestinal Mucosa / drug effects*,  metabolism
Leukotrienes / biosynthesis*,  blood,  metabolism
Male
Osteoarthritis / drug therapy,  metabolism,  veterinary*
Prostaglandins / biosynthesis*,  blood,  metabolism
Pyrazoles / pharmacology
Sulfones / pharmacology
Synovial Fluid / metabolism
Thiazines / pharmacology
Thiazoles / pharmacology
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Leukotrienes; 0/Prostaglandins; 0/Pyrazoles; 0/Sulfones; 0/Thiazines; 0/Thiazoles; 103475-41-8/tepoxalin; 189954-96-9/firocoxib; 71125-38-7/meloxicam; 96-48-0/4-Butyrolactone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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