Experimental models used to investigate the differential inhibition of cyclooxygenase-1 and cyclooxygenase-2 by non-steroidal anti-inflammatory drugs

Abstract

Numerous in vitro assays have been developed for testing and comparing the relative inhibitory activities of non-steroidal anti-inflammatory drugs against cyclooxygenase (COX)-1 and COX-2. Despite variability among these systems, which precludes direct comparison of data, analysis of the ratio of inhibition of COX-1 to COX-2 by non-steroidal anti-inflammatory drugs, suggests inhibitors can be classified based on their COX selectivity. Standard non-steroidal anti-inflammatory drugs can be considered nonselective; compounds such as meloxicam and nimesulide can be classified as COX-2 preferential; and compounds such as SC 58125 and L-754,337 are selective for COX-2. Although in vitro systems are important for characterizing COX-1 and COX-2 inhibitory activity, the clinical relevance of these data should be considered carefully. The level of inhibition of COX-1 and COX-2, in vivo at a given dose in patients, cannot be predicted from in vitro data alone. The pharmacokinetic properties of each compound, including plasma levels, distribution and binding to plasma proteins, have to be taken into account. Human pharmacology studies concentrating on the inhibition of prostanoid synthesis in target tissues are of paramount importance in determining the clinical relevance of COX-2 selectivity.

Evolution of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Cyclooxygenase (COX) Inhibition and Beyond

“…Based on IC 50 values for both the COX-1 and COX-2 isoforms, COX-2 selectivity (ratio of COX-1 IC 50 /COX-2 IC 50 = Selectivity Index; SI) has been derived, which can be used to compare COX inhibition and selectivity data for diverse classes of COX inhibitors. Some examples of in vitro COX inhibition assay systems utilize purified/recombinant enzymes, or various cell lines obtained from either human or animal sources (84,85). NSAIDs that are weak inhibitors of both 5-Aminosalicylic acid, sodium isoforms salicylate, nabumetone, sulfasalazine ___________________________________________________________________________________ Each of these assay systems have their benefits and drawbacks.…”

A Brief Overview of the Coxib Drugs in the Veterinary Field

“…This indicates the drug selectivity for COX-2 and it is determined through calculation of the inhibitory concentration (IC 50 ) COX-1:COX-2 ratio (Bergh and Budsberg, 2005;Vane and Warner, 2000). However, these ratios have not been fully quantified and ratios for the same compound can be inconsistent, as the assays used were considerably different (Livingston, 2000;Pairet and Ryn, 1998).…”

The Effect of Plant Secondary Metabolites on Lipid Peroxidation and Eicosanoid Pathway

“…Induction of inflammatory respond also differs, and in most cases is performed by bacterial lipopolysaccharide, various cytokines and tumour necrosis factor. Different techniques are used for detection of enzymatic activity, such as different chromatographic techniques (TLC, HPLC-UV), as well as EIA [19,34].…”