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老年人的药物代谢动力学及毒理学问题。

ADME-tox issues for the elderly.

作者信息

Hilmer Sarah N

机构信息

Royal North Shore Hospital, Ward 11C Main Building, Pacific Highway, St Leonards NSW 2065, Australia.

出版信息

Expert Opin Drug Metab Toxicol. 2008 Oct;4(10):1321-31. doi: 10.1517/17425255.4.10.1321.

Abstract

BACKGROUND

The elderly, defined as people aged >65 years, are a heterogeneous population. With increasing age there is increased prevalence of disease for which medication may be indicated and increased drug toxicity.

OBJECTIVE/METHODS: This review of the published scientific and clinical data on absorption, distribution, metabolism, excretion and toxicity (ADME-tox) in old age informs prescribers and drug developers of age-related factors that determine drug dose, safety and efficacy.

RESULTS/CONCLUSION: Increased inter-individual variability is a major feature of toxicology in old age. Changes in ADME-tox associated with normal ageing are currently better described than changes in the frail aged. Reduced hepatic and renal clearance are the most significant toxicokinetic changes seen in normal ageing. Drug toxicity in old age is influenced by changes in the quantity, affinity and responsiveness of drug targets, physiologic reserve and response to injury. Further investigation of the effects of medications on cognitive and physical functions in older adults is required.

摘要

背景

老年人定义为年龄大于65岁的人群,是一个异质性群体。随着年龄增长,需要药物治疗的疾病患病率增加,药物毒性也增加。

目的/方法:本综述对已发表的关于老年人吸收、分布、代谢、排泄和毒性(ADME-tox)的科学和临床数据进行了分析,旨在向开处方者和药物研发人员介绍决定药物剂量、安全性和疗效的年龄相关因素。

结果/结论:个体间变异性增加是老年毒理学的一个主要特征。与正常衰老相关的ADME-tox变化目前比体弱老年人的变化描述得更好。肝和肾清除率降低是正常衰老中最显著的毒代动力学变化。老年药物毒性受药物靶点数量、亲和力和反应性、生理储备以及对损伤的反应变化影响。需要进一步研究药物对老年人认知和身体功能的影响。

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