衰弱对药代动力学影响的新进展:最新研究进展。

New Horizons in the impact of frailty on pharmacokinetics: latest developments.

机构信息

Kolling Institute, Royal North Shore Hospital, University of Sydney, St Leonards NSW, Australia.

Centre for Medicine Use and Safety, Monash University, Parkville, VIC, Australia.

出版信息

Age Ageing. 2021 Jun 28;50(4):1054-1063. doi: 10.1093/ageing/afab003.

Abstract

Frail older people have a high prevalence of drug use and are susceptible to adverse drug reactions. The physiological changes of frailty are likely to affect pharmacokinetics and pharmacodynamics. We reviewed the methods and findings of published studies of pharmacokinetics in frailty. Nine studies describing pharmacokinetics and an additional three of pharmacokinetic pathways in frail older people were identified. Most pharmacokinetic studies investigated a single administration of a medication, dose or formulation, in small populations, often with limited representation of males or females, and applied variable definitions of frailty. Pharmacokinetic sampling designs generally utilised saturated sampling followed by analysis based on the trapezoidal rule for area under the curve, with more recent studies using sparser sampling and more sophisticated modelling to obtain individual and population values of all pharmacokinetic parameters. Overall, the pharmacokinetic studies reported only small changes in some parameters for some drugs with frailty, with the most consistent change reduced hepatic clearance in frail older people. Recommendations for future studies of pharmacokinetics in frailty include (i) standard objective definitions of frailty; (ii) larger studies including people with mild, moderate and severe frailty; (iii) population pharmacokinetic modelling to allow sparser sampling and consideration of multiple influences on pharmacokinetics; (iv) physiologically based modelling as the physiology of frailty emerges and (v) longitudinal pharmacokinetic studies of chronic drug therapy from middle to old age and from robust to pre-frail to frail, including pre-clinical studies. These data, accompanied by pharmacodynamics data in frailty, will inform safe, effective prescribing for frail older people.

摘要

虚弱的老年人普遍存在药物使用情况,且易发生药物不良反应。虚弱的生理变化可能会影响药代动力学和药效动力学。我们回顾了已发表的关于虚弱人群药代动力学研究的方法和结果。确定了 9 项描述虚弱老年人药代动力学的研究和另外 3 项关于药代动力学途径的研究。大多数药代动力学研究都调查了单次给予药物、剂量或制剂在小人群中的情况,通常男性或女性的代表性有限,并且应用了不同的虚弱定义。药代动力学采样设计通常采用饱和采样,然后根据梯形规则对曲线下面积进行分析,最近的研究则采用更稀疏的采样和更复杂的建模来获得所有药代动力学参数的个体和群体值。总体而言,这些药代动力学研究仅报告了一些药物的一些参数有轻微变化,而最一致的变化是虚弱老年人肝清除率降低。关于虚弱人群药代动力学研究的建议包括:(i)标准客观的虚弱定义;(ii)包括轻度、中度和重度虚弱人群在内的更大规模研究;(iii)群体药代动力学建模,以允许更稀疏的采样,并考虑对药代动力学的多种影响;(iv)随着虚弱生理学的出现,采用基于生理学的建模;(v)从中年到老年,从强壮到衰弱前到衰弱进行慢性药物治疗的纵向药代动力学研究,包括临床前研究。这些数据,伴随着虚弱人群的药效动力学数据,将为虚弱老年人的安全、有效用药提供信息。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索