Meloxicam does not affect the antiplatelet effect of aspirin in healthy male and female volunteers.

This study determined if meloxicam, a selective cyclooxygenase (COX)-2 inhibitor, interferes with the antiplatelet effect of aspirin using platelet aggregation and thromboxane (Tx) B(2) endpoints in healthy volunteers. Eight male and 8 female volunteers participated in this open-label, randomized, two-treatment, two-way crossover trial. Treatment 1 was meloxicam (15 mg qd) over 4 days, and then aspirin (100 mg qd) was ingested 2 hours after meloxicam for an additional 7 days.

Designing selective COX-2 inhibitors: molecular modeling approaches.

Molecular modeling approaches have been successfully used to gain insight into the molecular mechanism of selective cyclooxygenase-2 (COX-2) inhibition. These approaches are based on X-ray structure data and results from structure-activity relationships and site-directed mutagenesis experiments. The recognition process of substrates and inhibitors by COX isoenzymes can be visualized by applying algorithms to describe local properties on the enzyme surface, thus allowing key differences in structure to be studied that may confer differential sensitivity to inhibitors.

COX-2 selectivity and inflammatory processes.

Increasing amounts of experimental and clinical data support the role of selective cyclooxygenase (COX)-2 inhibition in anti-inflammatory processes and the involvement of COX-1 inhibition in the side effects associated with non steroidal anti-inflammatory drug use. This review will focus on the differences in the structure of the COX-1 and COX-2 molecules, particularly the active site and how they are bound by various NSAIDs to achieve COX-2 selectivity. This COX-2 selectivity will then be characterized in pharmacological assays in vitro and in animal models in vivo.

Differential inhibition of cyclooxygenases-1 and -2 by meloxicam and its 4'-isomer.

Objective And Design: Two structurally related compounds, meloxicam (Mel) and its structural 4'-isomer (4'-Mel), were compared to examine the role of a slightly different chemical structure on cyclooxygenase (COX) selectivity in in vitro and in vivo experimental models.

Material Or Subjects: In vitro studies were performed using human whole blood obtained from healthy volunteers, in vivo studies were performed in rats.

Treatment: A concentration-response curve was obtained in the whole blood assay for Mel, 4'-Mel, indomethacin, piroxicam and diclofenac.

Effect of structural modification of enol-carboxamide-type nonsteroidal antiinflammatory drugs on COX-2/COX-1 selectivity.

Meloxicam (5), an NSAID in the enol-carboxamide class, was developed on the basis of its antiinflammatory activity and relative safety in animal models. In subsequent screening in microsomal assays using human COX-1 and COX-2, we discovered that it possessed a selectivity profile for COX-2 superior to piroxicam and other marketed NSAIDs. We therefore embarked on a study of enol-carboxamide type compounds to determine if COX-2 selectivity and potency could be dramatically improved by structural modification.