The Association of Age and Frailty with Paracetamol Conjugation in Man

• Published in: Age and ageing Vol. 19; no. 6; pp. 419 - 424
• Main Authors: WYNNE, H. A., COPE, L. H., HERD, B., RAWLINS, M. D., JAMES, O. F. W., WOODHOUSE, K. W.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.11.1990; Oxford Publishing Limited (England)
• Subjects: Acetaminophen; Acetaminophen - pharmacokinetics; Adolescent; Adult; Aged; Aging; Aging (Biology); Aging - metabolism; Aging - pathology; Drug metabolism; Drugs; Frail Elderly; Humans; Liver; Liver - metabolism; Liver - pathology; Male; Medical disorders; Medical research; Middle Aged; Older people; Organ Size; Pharmacokinetics; Physiological aspects
• ISSN: 0002-0729; 1468-2834
• DOI: 10.1093/ageing/19.6.419

The association of age, physical frailty and liver size upon hepatic conjugation reactions was studied using paracetamol as a model drug. Nineteen fit subjects (mean age 26 years), 20 fit subjects (mean age 73 years), and eight frail, hospitalized subjects (mean age 82 years) were recruited. Paracetamol clearance expressed in terms of body weight was significantly lower in the fit elderly than in the fit young subjects, and was lowest in the frail elderly subjects (p<0.01). There was no difference in paracetamol clearance expressed per unit volume of liver between the fit young and fit elderly subjects but it was significantly reduced in the frail subjects. Although the partial metabolic clearance to paracetamol sulphate was preserved per unit volume of liver with ageing and frailty, the partial metabolic clearance to paracetamol glucuronide per unit volume of liver was markedly reduced in the frail elderly (p<0.01) when compared with the fit subjects. These results show that age-associated changes in paracetamol clearance are attributable to both changes in liver volume and in general health. The findings underline the important influences of the elderly person's physical state upon drug clearance.