Effect of age on the pharmacokinetics of tenoxicam in comparison to other non-steroidal anti-inflammatory drugs (NSAIDs)

Abstract

Investigations have shown that elderly patients have an increased sensitivity to the effects of non-steroidal anti-inflammatory drugs (NSAIDs) with a concomitant higher frequency of side-effects. Several explanations for such an observation are possible including altered receptor responsiveness or changes in absorption and disposition of a drug. From a literature survey it becomes clear that the rate and extent of NSAID absorption do not appear to be changed to a clinically significant degree in the elderly patient. Most NSAIDs are eliminated predominantly by hepatic metabolism and metabolic clearance therefore controls their elimination and accumulation upon chronic dosage. Differences in the dependence of these disposition processes on age exist between the commonly used NSAIDs. In our studies with tenoxicam, steady-state concentrations and accumulation factors did not differ in elderly subjects from those observed in a young population. Therefore, no dosage adjustment of this drug is necessary in elderly patients to achieve similar plasma concentrations following standard dosing in young subjects. Disposition processes of propionic acid derivatives seem to be more affected by advanced age as shown by reports in the literature. Alterations in plasma protein binding, with an increased free fraction of the drug subsequent to changes in serum albumin concentrations were reported with naproxen and salicylates in the aged population. Similarly, ketoprofen and ibuprofen clearance were significantly lower in the elderly than in young volunteers, and an accumulation of naproxen was reported in the elderly after multiple dosing.