Clinical relevance of nonsteroidal anti-inflammatory drug pharmacokinetics

Only recently have the pharmacokinetic characteristics of nonsteroidal anti-inflammatory drugs (NSAIDs) been recognized as decisive factors in understanding the effects and side effects of these drugs. The accumulation of NSAIDs in inflamed tissue is central to the anti-inflammatory action, whereas high drug concentrations in the gastrointestinal tract wall, kidneys, blood, and liver may be major contributing factors to the incidence and severity of side effects. Also, variations in pharmacokinetic handling of NSAIDs by different patients may contribute considerably to differences in therapeutic response. An evaluation of the response-related pharmacokinetics of the three most widely used NSAIDs, diclofenac, indomethacin, and piroxicam, shows some obvious reasons for these differences: The onset of absorption and the bioavailability of diclofenac can vary considerably, and relevant inter-patient differences are found in the terminal plasma half-life of indomethacin and piroxicam. The variability in these parameters may contribute significantly to the observed variations in clinical response and to the incidence of unwanted drug effects.