Factors determining efficacy of NSAIDs

This article reviews the efficacy of NSAIDs and their pharmacokinetic and pharmacodynamic properties. The assumption that classic pharmacokinetic dose/plasma concentration response relationships can be applied to NSAIDs has tenuous support in the biomedical literature. Comparative efficacy studies, using ASA and indomethacin as the standards for comparison, ignore the fact that the major outcome variables are subjective responses among patients, not among drugs. Comparing inhibition of platelet malonyldialdehyde, synovial drug concentrations, urinary prostaglandin metabolites, and plasma free and total concentration with the clinical outcome provides no guidelines to serve as predictors of response. The individual agents, indomethacin, salicylates, sulindac, piroxicam, and naproxen, illustrate the complexities of NSAID pharmacotherapy. Recent proliferation of newer NSAIDs will not add significantly to the efficacy of these agents in the treatment of pain and inflammatory disease states. However, knowledge of pharmacokinetic population parameters for the individual NSAIDs will increase the likelihood of therapeutic success and diminish the possibilities for adverse reactions.