Wynne H A, Cope L H, Herd B, Rawlins M D, James O F, Woodhouse K W
Geriatric Pharmacology Unit, University of Newcastle upon Tyne.
Age Ageing. 1990 Nov;19(6):419-24. 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 less than 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 less than 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.
以对乙酰氨基酚作为模型药物，研究了年龄、身体虚弱程度和肝脏大小与肝脏结合反应之间的关系。招募了19名健康受试者（平均年龄26岁）、20名健康受试者（平均年龄73岁）和8名体弱的住院受试者（平均年龄82岁）。以体重表示的对乙酰氨基酚清除率在健康老年人中显著低于健康年轻受试者，在体弱老年人中最低（p<0.01）。健康年轻受试者和健康老年受试者每单位肝脏体积的对乙酰氨基酚清除率没有差异，但在体弱受试者中显著降低。尽管随着年龄增长和身体虚弱，每单位肝脏体积对硫酸对乙酰氨基酚的部分代谢清除率保持不变，但与健康受试者相比，体弱老年人每单位肝脏体积对乙酰氨基酚葡萄糖醛酸苷的部分代谢清除率显著降低（p<0.01）。这些结果表明，与年龄相关的对乙酰氨基酚清除率变化归因于肝脏体积和总体健康状况的变化。这些发现强调了老年人身体状态对药物清除的重要影响。
