Tests capable of differentiating the inhibition of COX-1 as opposed to COX-2 have flourished since the discovery of the inducible isoenzyme of cyclooxygenase (COX-2)

Journal/Book: Z Rheumatol 1998; 57 Suppl. 1: 12 (V 42). 1998;

Abstract: Boehringer Ingelheim Pharma KG The clinical importance of this differentiation is based upon the hypothesis that the anti-inflammatory effects of non-steroidal anti-inflammatory drugs (NSAIDs) are dependent upon their inhibition of the inducible isoform COX-2 whereas inhibition of constitutive COX-1 is responsible for their gastric and renal side effects (2). Thus to optimize the therapeutic effect while minimizing the side effects agents that can selectively inhibit COX-2 are desirable. This has led to an array of in vitro assay systems with which to characterize NSAIDs for their COX-2 selectivity. Unfortunately experience has shown that the experimental conditions may markedly affect the outcome of such assessments. The source of enzymes COX-1 and COX-2 (i. e. human or animal) or the type of cell system used (intact normal cells or transfected cell lines) comprise an initial important consideration and by itself leads to variable results. Additional methodological considerations including the method of enzyme preparation (purified enzymes microsomal or whole cell assays) as well as the COX-2 inducing agent employed have also been shown to be important variables. Furthermore the incubation time of a given system with a test drug an inducing agent or with arachidonic acid (and the concentration of arachidonic acid) are important. Even the presence of protein in the medium and its concentration can play an important role. Typically the IC50 for COX-1 and COX-2 inhibition has been defined using such systems and a ratio calculated and defined as a measure of selectivity. Depending on the test systems used however conflicting and confusing comparisons have arisen. ... le

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