Antipyrine disposition and liver size in the elderly

Abstract

This study has examined the contribution of decrease in liver size to the decline in drug metabolising capacity which occurs with ageing. Liver volume and antipyrine kinetics were measured in two groups of healthy individuals aged 20 to 29 years and 75 to 86 years and in a group of hospitalised patients aged 70 to 89 years. Liver volume was reduced in both groups of elderly people compared to the young group. Antipyrine plasma half-life was prolonged and antipyrine clearance was reduced in the group of elderly normal individuals. In this group the index--antipyrine clearance per unit liver volume--was also reduced in comparison to that of the young group. Measurements of antipyrine elimination in the hospitalised elderly group did not differ significantly from those in the young group. It is concluded that both decreased liver mass and decreased hepatic enzyme activity contribute to the impairment of drug oxidation which occurs in the elderly and which may warrant a reduction in dosage of some drugs. However, differences have been demonstrated between groups of elderly people suggesting that under certain circumstances standard doses of such drugs may be normally tolerated.

Increased Serum Salicylate Metabolites with Age in Patients Receiving Chronic Acetylsalicylic Acid Therapy

“…Although serum creatinine did not correlate with serum GA or SUA in these patients, there is a well-defined fall in creatinine clearance with age that is not re flected by serum creatinine [Kampmann and Molholm, 1979], Cuny et al [1979] reported prolongation of SA elimination half times in the elderly, which suggests that enhanced rate of production of salicylate metabolites is not likely. Although age-related changes in drug distribution can significantly affect their se rum concentration [Klotz et al, 1975;Swift et al, 1978], we presently have no evidence that this mechanism can explain our observa tions.…”

Theophylline pharmacokinetics in advanced age.

“…Frequently the elderly are institutionalized, often with multiple pathologies, while the controls are in independent and community living. Swift et al (1978) have shown that metabolic rates can be significantly dependent on such environmental differences. Even when differences in lifestyle and pathology are minimized, a multitude of environmental and genetic factors such as smoking, drinking, Cusack etal.…”

Age‐related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications

“…Several studies have shown significant reductions in the clearance of many drugs metabolized by phase-1 pathways in the liver [78,79]. The main factor is probably represented by the age-related changes in liver size and hepatic blood flow as the activity of drug metabolizing enzymes is preserved [80].…”