Variability in response to NSAIDs: what progress?

Abstract

Little further work has established the nature and importance of variability in response to NSAIDs despite the phenomenon being identified by Huskisson in 1976. The following questions remain unanswered: the proportion of individuals who display marked variability in responses to different NSAIDs; reproducibility of individual responses over repeated exposures; the influence of various musculoskeletal disorders on the level of variability in response; and the importance of pharmacokinetic or pharmacodynamic mechanisms. Data continue to accumulate that there is a weak relationship between concentration of NSAIDs in plasma and degree of efficacy in RA and now OA and acute pain states, as well as with the incidence of toxicity, notably GI bleeding. The efficacy relationship may resemble a rectangular hyperbola with a steep slope upwards. None of the proposed mechanisms of action of NSAIDs additional to the universal ability to inhibit prostaglandin synthesis, which have been suggested as possible causes of response differences between drugs, has been linked rigourously to responses in individual patients. Systematic work linking clinical responses to pharmacokinetic parameters and pharmacodynamic mechanisms is required to understand variability of responses to NSAID therapy.