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NSAIDs: Therapeutic use and variability of response in adults

Daniel H Solomon, MD, MPH
Section Editor
Daniel E Furst, MD
Deputy Editor
Paul L Romain, MD


A variety of nonsteroidal antiinflammatory drugs (NSAIDs) are readily available (at least 20 in the United States and more elsewhere) and are widely used throughout the world (table 1). In the United States, aspirin, ibuprofen, naproxen, and ketoprofen can also be obtained without prescription. Each year, approximately 60 million NSAID prescriptions are written, with the number of prescriptions for older patients approximately 3.6-fold higher than that for younger patients [1,2].

Questions concerning the variability of response to the effects of the different NSAIDs have led to efforts to understand the potential and real differences between these drugs. All NSAIDs appear to be absorbed completely, have negligible first pass hepatic metabolism, are tightly bound to albumin, and have small volumes of distribution. Patients with hypoalbuminemia may, therefore, have higher free serum concentrations of drug.

However, it is unclear whether the blood level of a NSAID is important in assessing its mode of action or its effectiveness, since protein-binding is saturable in the normal dose range for several NSAIDs. As a result, increases in dose may not lead to increases in steady state concentration of the drug. At equipotent doses, the clinical efficacy of the various NSAIDs in patient populations is similar [3]; in contrast, individual responses are highly variable [4].

Some of the observed individual differences with specific NSAIDs are particularly evident with respect to toxicity [3]. As an example, it is not unusual for indomethacin to induce headaches after a single dose in some patients. More commonly, individual patients have more symptoms or signs of gastrointestinal toxicity with one NSAID than with another [5]. Some differences in toxicity may be explained by variations in absorption, distribution, and metabolism. Differences in the mode of action may be important as well.

This topic will review the issues surrounding the differences in response to the various NSAIDs [4,6]. Clinical considerations in the use of these agents will also be discussed, while the different types of toxicity that may be seen with both nonselective and COX-2 selective NSAIDs are presented separately. (See "Nonselective NSAIDs: Overview of adverse effects" and "Overview of selective COX-2 inhibitors".)


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Literature review current through: Sep 2016. | This topic last updated: Jan 27, 2016.
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