Abstract | BACKGROUND AND PURPOSE: EXPERIMENTAL APPROACH: KEY RESULTS:
Oral administration of JNJ 26993135 (5, 15 and 30 mg kg(-1), twice a day) dose-dependently reduced both the extent and intensity of the colonic inflammatory damage observed 3 days after TNBS challenge. JNJ 26993135 also dose-dependently reduced the elevated colonic levels of LTB(4), as well as the inflammatory biomarkers, MPO, IL-6 and TNF-alpha. This dosing regimen was supported by the pharmacokinetic profile of JNJ 26993135, along with the demonstration of the inhibition of ex vivo production of LTB(4) in whole blood following oral administration. CONCLUSIONS AND IMPLICATIONS:
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Authors | B J R Whittle, C Varga, A Berko, K Horvath, A Posa, J P Riley, K A Lundeen, A M Fourie, P J Dunford |
Journal | British journal of pharmacology
(Br J Pharmacol)
Vol. 153
Issue 5
Pg. 983-91
(Mar 2008)
ISSN: 0007-1188 [Print] England |
PMID | 18157165
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Benzothiazoles
- Enzyme Inhibitors
- Interleukin-6
- Piperidines
- Tumor Necrosis Factor-alpha
- 1-(4-(benzothiazol-2-yloxy)benzyl)piperidine-4-carboxylic acid
- Trinitrobenzenesulfonic Acid
- Peroxidase
- Epoxide Hydrolases
- leukotriene A4 hydrolase
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Topics |
- Administration, Oral
- Animals
- Benzothiazoles
(administration & dosage, pharmacokinetics, pharmacology)
- Colitis
(chemically induced, drug therapy, physiopathology)
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Drug Delivery Systems
- Enzyme Inhibitors
(administration & dosage, pharmacokinetics, pharmacology)
- Epoxide Hydrolases
(antagonists & inhibitors)
- Inflammation
(drug therapy, etiology)
- Interleukin-6
(metabolism)
- Male
- Peroxidase
(drug effects, metabolism)
- Piperidines
(administration & dosage, pharmacokinetics, pharmacology)
- Rats
- Rats, Wistar
- Severity of Illness Index
- Trinitrobenzenesulfonic Acid
- Tumor Necrosis Factor-alpha
(drug effects, metabolism)
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