The disposition of antipyrine and its metabolites in young and elderly healthy volunteers.

Abstract

1 Oxidative metabolism of antipyrine (AP) was compared in 11 elderly (greater than 65 years) and 12 young (less than 40 years) volunteers. All subjects were non‐smokers, consumed little if any alcohol and were in good health. 2 After a single dose of AP 500 mg, its clearance from saliva and profiles of the parent drug and its major metabolites in urine were determined using high‐performance liquid chromatography. 3 Mean total AP clearance from saliva was lower in the elderly (P less than 0.05). Mean weight‐normalised volume of distribution was also smaller (P less than 0.01) so that elimination half‐life in the elderly was not significantly different from that in the young. 4 The percentage dose excreted in 48 h urine as norantipyrine (NORA) and its clearance for production were lower in the elderly (P less than 0.001 and P less than 0.01 respectively). Urinary 3‐hydroxymethylantipyrine (HMA) and free antipyrine were present in greater quantities in 48 h urine in the elderly (P less than 0.001 and P less than 0.05) while the amounts of 4‐hydroxyantipyrine (OHA) were almost identical in the two age groups. 5 The findings suggest that there is a selective impairment of N‐demethylation in the elderly which may have important implications for dosage of elderly patients with drugs metabolised by this route.