Playfer J R, Powell C, Evans D A
Age Ageing. 1977 May;6(2):89-95. doi: 10.1093/ageing/6.2.89.
Genetic factors are known to be of importance in determining the rate of biotransformation of foreign compounds in the liver. Adverse reactions to drugs are increased and pharmacokinetic parameters altered with age. In the present study, the effect of age on plasma paroxonase activity is studied. Paroxonase is a hepatically synthesized enzyme whose activity is almost entirely determined by genetic factors. It therefore serves as a model to determine whether changes in the frequency or expression of genes could explain the altered responses to drugs observed with age. The frequency distribution for paroxonase activity for 186 elderly people is closely similar to that obtained from 190 blood transfusion volunteers and 189 family members. Paroxonase activity, as with all other previously investigated pharmacogenetic polymorphisms, is unchanged with age. The hypothesis is put forward that genetic determinants of drug metabolism remain unchanged with age.
已知遗传因素在决定肝脏对外源化合物的生物转化速率方面具有重要意义。药物不良反应会随着年龄增长而增加，药代动力学参数也会发生改变。在本研究中，研究了年龄对血浆对氧磷酶活性的影响。对氧磷酶是一种肝脏合成的酶，其活性几乎完全由遗传因素决定。因此，它可作为一个模型，来确定基因频率或表达的变化是否能够解释随着年龄增长所观察到的对药物反应的改变。186名老年人的对氧磷酶活性频率分布与190名输血志愿者及189名家庭成员的频率分布非常相似。与所有其他先前研究的药物遗传多态性一样，对氧磷酶活性不会随年龄而改变。由此提出假说：药物代谢的遗传决定因素不会随年龄而改变。
