JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
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Emerging evidence in NSAID pharmacology: important considerations for product selection.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment of pain and inflammation. Emerging pharmacokinetic and pharmacodynamic evidence in NSAID pharmacology provides important criteria for selecting an appropriate NSAID. The inhibition of COX enzymes by NSAIDs affects physiologic functions in the gastrointestinal, cardiovascular, and renal systems. Of the 2 principal types of COX enzymes, COX-1 and COX- 2, the pain-relieving (anti-hyperalgesia) effects of NSAIDs are driven mainly by the inhibition of COX-2. Commonly, NSAIDs are categorized by in vitro selectivity (ie, the ratio of the NSAID concentrations required for inhibition of COX-1 and COX-2) as selective or nonselective. Theoretically, the concept of selectivity is convenient; however, the actual relative inhibition of COX-1 and COX-2 isoenzymes measured in vitro is dose-dependent. As a result, the predicted in vivo reduction of prostanoidinduced hyperalgesia and the expected adverse effects of an NSAID are dose dependent. Individual NSAIDs also differ on pharmacokinetic and pharmacodynamic parameters such as the absorption, time to availability of drug at the site of inflammation, and persistence at the site of inflammation. NSAIDs with longer half-life durations may offer longer durations of analgesia due to continued COX enzyme inhibition, but may provide less opportunity for recovery of COX activity between doses than NSAIDs with shorter half-lives. Understanding these pharmacokinetic and pharmacodynamic factors informs selection of an appropriate NSAID among this heterogeneous class of drugs.

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