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The evaluation of the COX‐2 selective inhibition of lumiracoxib, a novel nonsteroidal anti‐inflammatory drug
Author(s) -
Furuie H.,
Murakami M.,
Matsuguma K.,
Ishibashi M.,
Tsukikawa H.,
Kimura M.,
Shishido A.,
Irie S.
Publication year - 2004
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2003.11.016
Subject(s) - tolerability , pharmacology , placebo , medicine , drug , pharmacokinetics , adverse effect , alternative medicine , pathology
[Objective] Lumiracoxib is a novel COX‐2 selective inhibitor and is expected to have a reduced incidence of upper gastrointestinal tract disorder involving COX‐1. This study evaluates the COX‐2 selective inhibition of lumiracoxib in healthy Japanese male subjects following single oral doses. [Method] This study was a single blind, placebo‐controlled, ascending single oral dose study. Plasma PK were determined by HPLC. Two PD markers were measured. For COX‐1, TxB2 activity was measured with serum. For COX‐2, heparinized blood samples were stimulated with LPS, incubated for 24 hours at 37°C, then applied to PGE2 (COX‐2 marker) assay with plasma. [Result] Plasma lumiracoxib PK in Japanese were found dose‐linear. TxB2 formation as a PD marker of COX‐1 inhibition was not inhibited by treatment, i.e., no meaningful difference in the PD response between lumiracoxib and placebo group, while PGE2 formation decreased in a dose‐dependent manner. Accordingly, there was no clear relationship between the plasma lumiracoxib concentration and the inhibition of TxB2 formation, while a clear correlation was observed between the plasma lumiracoxib concentration and the inhibition of PGE2 formation. These PK/PD characters were consistent with those in Western population studied separately. [Conclusion] Lumiracoxib selectively inhibits COX‐2 and is expected to improve tolerability with respect to upper gastrointestinal tract disorder caused by COX‐1 inhibition. Clinical Pharmacology & Therapeutics (2004) 75 , P5–P5; doi: 10.1016/j.clpt.2003.11.016