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Pharmacodynamic behaviour of the selective cyclooxygenase-2 inhibitor lumiracoxib in the lipopolysaccharide-stimulated rat air pouch model.

Esser, Ronald and Miserendino-Molteni, Rocca and Sharr, Michele and Zhang, Xiaoli and Porter, Wilma and Ramos, Luis and Cramer, Jeffrey and Zhuang, Shumin and Georgieva, Anna and Maniara, Wieslawa (2005) Pharmacodynamic behaviour of the selective cyclooxygenase-2 inhibitor lumiracoxib in the lipopolysaccharide-stimulated rat air pouch model. European Journal of Pharmaceutical Sciences : official journal of the European Federation for Pharmaceutical Sciences, 25 (1). pp. 25-30. ISSN 0928-0987

Abstract

PURPOSE: To investigate the pharmacodynamic behaviour of the selective cyclooxygenase-2 inhibitor, lumiracoxib, in the rat air pouch. METHODS: Air pouches were injected with lipopolysaccharide to stimulate prostaglandin E2 (PGE2) production 1h after lumiracoxib treatment. Pouch fluid samples were collected 6 or 24 h after lumiracoxib administration to measure PGE2 levels. Lumiracoxib concentrations in pouch fluid and plasma were measured by mass spectrometry. RESULTS: Oral administration of lumiracoxib resulted in dose-dependent inhibition of PGE2 production 6 and 24 h post-dose. The estimated ED50 values for inhibition of PGE2 production were 0.1 and 2.0 mg/kg at 6 and 24 h, respectively. Lumiracoxib concentrations in plasma and pouch fluid increased in proportion to dose. There was a strong positive correlation between lumiracoxib concentrations in plasma and pouch fluid compartments. Lumiracoxib concentrations were higher in plasma than in pouch fluid 6 h post-dose, but at 24 h post-dose, pouch fluid concentrations were > or =4-fold greater than plasma concentrations. CONCLUSIONS: Lumiracoxib readily enters the air pouch and persists in this extravascular compartment for a longer period of time than in plasma. This distribution profile may contribute to the ability of lumiracoxib to inhibit PGE2 production up to 24 h after dosing.

Item Type: Article
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Additional Information: author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
Keywords: Lumiracoxib; Pharmacodynamics; Cyclooxygenase-2; Prostaglandin E2
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Date Deposited: 14 Dec 2009 13:56
Last Modified: 31 Jan 2013 01:11
URI: https://oak.novartis.com/id/eprint/643

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