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Preclinical pharmacology of lumiracoxib: a novel selective inhibitor of cyclooxygenase‐2
Author(s) -
Esser Ronald,
Berry Carol,
Du Zhengming,
Dawson Janet,
Fox Alyson,
Fujimoto Roger A,
Haston William,
Kimble Earl F,
Koehler Julie,
Peppard Jane,
Quadros Elizabeth,
Quintavalla Joseph,
Toscano Karen,
Urban Laszlo,
Duzer John,
Zhang Xiaoli,
Zhou Siyuan,
Marshall Paul J
Publication year - 2005
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0706078
Subject(s) - pharmacology , diclofenac , cyclooxygenase , analgesic , oral administration , medicine , antipyretic , thromboxane b2 , chemistry , enzyme , biochemistry , platelet
1 This manuscript presents the preclinical profile of lumiracoxib, a novel cyclooxygenase‐2 (COX‐2) selective inhibitor. 2 Lumiracoxib inhibited purified COX‐1 and COX‐2 with K i values of 3 and 0.06 μ M , respectively. In cellular assays, lumiracoxib had an IC 50 of 0.14 μ M in COX‐2‐expressing dermal fibroblasts, but caused no inhibition of COX‐1 at concentrations up to 30 μ M (HEK 293 cells transfected with human COX‐1). 3 In a human whole blood assay, IC 50 values for lumiracoxib were 0.13 μ M for COX‐2 and 67 μ M for COX‐1 (COX‐1/COX‐2 selectivity ratio 515). 4 Lumiracoxib was rapidly absorbed following oral administration in rats with peak plasma levels being reached between 0.5 and 1 h. 5 Ex vivo , lumiracoxib inhibited COX‐1‐derived thromboxane B 2 (TxB 2 ) generation with an ID 50 of 33 mg kg −1 , whereas COX‐2‐derived production of prostaglandin E 2 (PGE 2 ) in the lipopolysaccharide‐stimulated rat air pouch was inhibited with an ID 50 value of 0.24 mg kg −1 . 6 Efficacy of lumiracoxib in rat models of hyperalgesia, oedema, pyresis and arthritis was dose‐dependent and similar to diclofenac. However, consistent with its low COX‐1 inhibitory activity, lumiracoxib at a dose of 100 mg kg −1 orally caused no ulcers and was significantly less ulcerogenic than diclofenac ( P <0.05). 7 Lumiracoxib is a highly selective COX‐2 inhibitor with anti‐inflammatory, analgesic and antipyretic activities comparable with diclofenac, the reference NSAID, but with much improved gastrointestinal safety.British Journal of Pharmacology (2005) 144 , 538–550. doi: 10.1038/sj.bjp.0706078