Faculty of Pharmacy, University of Sydney, Sydney, NSW 2006, Australia.
J Gerontol A Biol Sci Med Sci. 2012 Feb;67(2):175-80. doi: 10.1093/gerona/glr118. Epub 2011 Aug 10.
Hepatic clearance plays a key role in determining the systemic exposure of drugs and metabolites, which in turn has a major effect on variability in the beneficial and adverse effects of medicines. Aging results in a number of significant changes in the human liver including reductions in liver blood flow, size, drug-metabolizing enzyme content, and pseudocapillarization. Drug metabolism is also influenced by comorbid disease, frailty, concomitant medicines, and (epi)genetics. These changes have the potential to alter the hepatic clearance of drugs but need to be interpreted in the context of the pharmacokinetic (and pharmacodynamic) characteristics of the drug of interest. There is growing evidence that the age-related changes in the liver not only result in a decrease in the hepatic clearance of unbound drug but also influence variability in response to medicines in older people.
肝脏清除率在确定药物及其代谢物的全身暴露中起着关键作用，而这反过来又对药物的有益和不良反应的变异性有重大影响。衰老会导致人体肝脏发生许多重大变化，包括肝血流量、肝脏大小、药物代谢酶含量和伪毛细血管化减少。药物代谢也受到合并疾病、虚弱、伴随药物和（表观）遗传学的影响。这些变化有可能改变药物的肝脏清除率，但需要结合感兴趣药物的药代动力学（和药效动力学）特征来解释。越来越多的证据表明，肝脏的衰老相关变化不仅导致未结合药物的肝脏清除率下降，而且还影响老年人对药物反应的变异性。
