Drugs & Aging

, Volume 32, Issue 12, pp 999–1008 | Cite as

Age-Related Changes in Hepatic Function: An Update on Implications for Drug Therapy

  • Joseph L. Tan
  • Jacques G. Eastment
  • Arjun Poudel
  • Ruth E. HubbardEmail author
Review Article


The accumulation of deficits with increasing age results in a decline in the functional capacity of multiple organs and systems. These changes can have a significant influence on the pharmacokinetics and pharmacodynamics of prescribed drugs. Although alterations in body composition and worsening renal clearance are important considerations, for most drugs the liver has the greatest effect on metabolism. Age-related change in hepatic function thereby causes much of the variability in older people’s responses to medication. In this review, we propose that a decline in the ability of the liver to inactivate toxins may contribute to a proinflammatory state in which frailty can develop. Since inflammation also downregulates drug metabolism, medication prescribed to frail older people in accordance with disease-specific guidelines may undergo reduced systemic clearance, leading to adverse drug reactions, further functional decline and increasing polypharmacy, exacerbating rather than ameliorating frailty status. We also describe how increasing chronological age and frailty status impact liver size, blood flow and protein binding and enzymes of drug metabolism. This is used to contextualise our discussion of appropriate prescribing practices. For example, while the general axiom of ‘start low, go slow’ should underpin the initiation of medication (titrating to a defined therapeutic goal), it is important to consider whether drug clearance is flow or capacity-limited. By summarising the effect of age-related changes in hepatic function on medications commonly used in older people, we aim to provide a guide that will have high clinical utility for practising geriatricians.


Hepatic Metabolism Drug Clearance Hepatic Clearance Frailty Status Liver Sinusoidal Endothelial Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Compliance with Ethical Standards

All authors contributed to this paper and all approved the final version. No funding was received for the preparation of this manuscript.

Joseph L. Tan, Jacques G. Eastment, Arjun Poudel, and Ruth E. Hubbard declare no conflicts of interests and compliance with ethical standards.


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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Joseph L. Tan
    • 1
  • Jacques G. Eastment
    • 1
  • Arjun Poudel
    • 2
  • Ruth E. Hubbard
    • 1
    Email author
  1. 1.Centre for Research in Geriatric Medicine, School of MedicineThe University of Queensland, Princess Alexandra HospitalBrisbaneAustralia
  2. 2.School of PharmacyThe University of QueenslandBrisbaneAustralia

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