Pharmacology and efficacy of cyclooxygenase (COX) inhibitors

Discussion of the pharmacology and efficacy of cyclooxygenase (COX) inhibition requires careful attention to the methodology used for making those comparisons. In vitro analysis of COX-2/COX-1 ratios requires consideration of the target tissues being examined, the details of incubation periods, outcome measures, and other parameters. Application of those data to the in vivo situation requires careful cognizance of pharmacokinetic factors such as clearance and serum half-life, protein binding, lipophilicity, and pKa. Proceeding from in vitro studies to efficacy studies also requires a careful consideration of methodology. Studies must be well controlled, of sufficient duration (≥12 weeks for rheumatoid arthritis), and, importantly, require equipotent dosing regimens. Equipotence may be hard to prove because in vitro and animal studies cannot predict equipotence in humans. Clinical studies are needed to prove equipotence. The obverse of efficacy is toxicity, and only with the knowledge of equipotent doses can toxicity be appropriately compared. Based on approximate equipotence, highly selective COX-2 inhibitors may cause fewer peptic ulcers and bleeds than drugs that are COX-1 preferential. COX-2 preferential (not highly selective) drugs may occupy a place between the two.