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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Non-steroidal anti-inflammatory analgesics other than salicylates.

The largest group of non-narcotic analgesics are the arylalkanoic acid derivatives, comprising derivatives of arylacetic acid, propionic acid, heteraryl acetic acid and indole acetic acid. Common to all of these drugs is their inhibition of prostaglandin biosynthesis, which contributes to their analgesic and other pharmacological properties as well as to their principal side effect, gastrointestinal irritation. Although these drugs all cause some gastric microbleeding, they do so to a lesser extent than aspirin. The arylalkanoic acid derivatives, as well as the anthranilic acid and oxicam derivatives, are peripherally acting as evidenced by their lack of activity in classical tests of central analgesic activity. After oral administration of these drugs, their peak plasma concentrations are generally attained in 1 to 3 hours; absorption is not generally influenced by food. Volume of distribution is mostly low (less than 0.2 L/kg) and protein binding is high (usually 95 to 99%). Elimination is by glucuronide formation for several of the propionic acid derivatives and generally by biotransformation for derivatives of arylacetic acid, indole and indene acetic acid, and the oxicams. The elimination half-life of the arylalkanoic acid derivatives is in most instances about 2 to 5 hours, although notable exceptions include carprofen (approximately equal to 20 h), fenbufen (10 h), naproxen (12-15 h) and sulindac (16 h for the active metabolite). The elimination half-life of indomethacin varies considerably between and within individuals. Piroxicam has the longest half-life, averaging 45 hours. The pharmacokinetic properties of the anthranilic acid derivatives (fenamates, glafenine) generally resemble those of the arylacetic acids. Few clinically significant drug interactions are associated with concomitant administration of the arylalkanoic acids or piroxicam and other drugs. Since the arylalkanoic acids are highly bound to plasma proteins (mainly albumin) there is a theoretical potential for displacement reactions with drugs that are used at plasma concentrations high enough to exceed the binding capacity of their own primary binding sites. However, such reactions have rarely been reported. Although the concomitant administration of aspirin and several of the propionic acid derivatives results in a significant decrease in the plasma concentration of the latter, the clinical significance of such interactions is uncertain and probably minimal.(ABSTRACT TRUNCATED AT 250 WORDS)[1]


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