INHIBITION OF CYCLOOXYGENASE-1 AND CYCLOOXYGENASE-2 - ANALYSIS OF IN-VITRO TEST SYSTEMS AND THEIR CLINICAL RELEVANCE

Numerous in vitro assay systems have been developed for testing and co mparing the relative inhibitory activities of nonsteroidal anti-inflam matory drugs (NSAIDs) against cyclooxygenase (COX)-1 and COX-2, the tw o COX isoforms responsible for prostaglandin biosynthesis. Despite var iability among these systems, which precludes direct comparison of dat a, analysis of the ratio of inhibition of COX-2 to COX-1 by NSAIDs sug gests that inhibitors can be classified based on their COX selectivity . Standard NSAIDs can be considered nonselective; compounds such as me loxicam, nimesulide, and etodolac can be classified as preferential CO X-2 inhibitors; other compounds currently under development are highly specific for COX-2. Although in vitro systems are important in charac terizing activity, the clinical relevance of these data should be care fully considered. Models based on in vitro data can be constructed and may be compared with, but are no substitute for, in vivo results when they become available.