Esser, Ronald, Miserendino-Molteni, Rocca, Sharr, Michele, Zhang, Xiaoli, Porter, Wilma, Ramos, Luis, Cramer, Jeffrey, Zhuang, Shumin, 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
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez... doi:10.1016/j.ejps.2005.01.014
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
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez... doi:10.1016/j.ejps.2005.01.014
Date Deposited:	14 Dec 2009 13:56
Last Modified:	31 Jan 2013 01:11
URI:	https://oak.novartis.com/id/eprint/643