Pharmacokinetics and irreversible binding of tolmetin and its glucuronic acid esters in the elderly.

In a previous study, the disposition and irreversible plasma protein binding of tolmetin have been described in young volunteers. Significant levels of tolmetin glucuronide and its isomer(s) were found in plasma, and irreversible binding was shown to occur in all subjects. In the present study, the pharmacokinetics and irreversible binding in 5 elderly volunteers are investigated after a single dose (400 mg) of tolmetin. No difference of physiological importance has been found, unless weight correction is employed, when compared with the young subjects. Very strong correlations were present between the level of binding and exposure to the glucuronide or its isomer. An elderly patient currently treated with tolmetin (400 mg b.i.d.) also participated in the study. The results show an accumulation of the irreversible binding to levels 4-17 times higher than after a single dose. Nevertheless, neither toxic nor allergic reactions have been observed in this patient.