A letter to the Lancet (S S Adams, 21 Nov 1987, 1204–5) points out that when the CSM adverse reactions data for the 11 NSAIDs cited in our table are ranked in descending order of toxicity, nearly all those with a long plasma elimination half-life of about 10 hours or more (for the drug + active metabolites) come at the top of the list. The other compounds have a short half-life, 4 hours or less. The table below shows the relevant CSM data rearranged in rank order, and the approximate half-lives of the drugs. Half-lives vary widely between patients and tend to be longer in the elderly. Toxicity is obviously not determined by slow elimination alone, but prolonged high concentrations of a drug in the tissues are likely to exacerbate any toxic effects. Short-acting drugs may allow some recovery between doses from the potentially damaging inhibition of prostaglandin synthesis at vulnerable sites, such as the gut and kidney. NSAIDs with a short half-life should therefore be preferred unless a somewhat longer action is needed to alleviate morning stiffness. Sustained-release forms of NSAIDs with an otherwise short half-life should also be used cautiously.
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