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 comparing the relative inhibitory activities of nonsteroidal anti-inflammatory drugs (NSAIDs) against cyclooxygenase (COX)- 1 and COX-2, the two COX isoforms responsible for prostaglandin biosynthesis. Despite variability among these systems, which precludes direct comparison of data, analysis of the ratio of inhibition of COX-2 to COX-1 by NSAIDs suggests that inhibitors can be classified based on their COX selectivity. Standard NSAIDs can be classified as preferential COX-2 inhibitors; other compounds currently under development are highly specific for COX-2. Although in vitro systems are important in characterizing activity, the clinical relevance of these data should be carefully considered. Models based on in vitro data can be constructed and maybe compared with, but are no substitute for, in vivo results when they become available.
Pairet
M
M
Department of Pulmonary Research (Atemwegsforschung), Boehringer Ingelheim Pharma KG, Ingelheim, Germany.