PHARMACOKINETICS AND IRREVERSIBLE BINDING OF TOLMETIN AND ITS GLUCURONIC-ACID ESTERS IN THE ELDERLY

In a previous study, the disposition and irreversible plasma protein b inding of tolmetin have been described in young volunteers. Significan t levels of tolmetin glucuronide and its isomer(s) were found in plasm a, and irreversible binding was shown to occur in all subjects. In the present study, the pharmacokinetics and irreversible binding in 5 eld erly volunteers are investigated after a single dose (400 mg) of tolme tin. 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 current ly treated with tolmetin (400 mg b. i. d.) also participated in the st udy. The results show an accumulation of the irreversible binding to l evels 4-17 times higher than after a single dose. Nevertheless, neithe r toxic nor allergic reactions have been observed in this patient.