Drug Metabolism in Older People--A Key Consideration in Achieving Optimal Outcomes With Medicines
Abstract
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.
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Metabolic changes associated with aging make older adults more sensitive to BZDs, increasing their risk of adverse events such as cognitive impairment, particularly in the domains of memory, learning, attention, and visuospatial ability.
“metabolic changes associated with aging make older adults more sensitive to BZDs, increasing their risk of adverse events such as cognitive impairment, particularly in the domains of memory, learning, attention, and visuospatial ability.92,171,172”
From Joint Clinical Practice Guideline on Benzodiazepine Tapering: Considerations When Risks Outweigh Benefits (2025) · cites this paper as [171]
Metabolic changes associated with aging, namely reduced hepatic clearance, may increase risk of adverse events and toxicity.
“metabolic changes associated with aging—namely, reduced hepatic clearance—may increase risk of adverse events and toxicity.171”
From Joint Clinical Practice Guideline on Benzodiazepine Tapering: Considerations When Risks Outweigh Benefits (2025) · cites this paper as [171]
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“171 As a result, the CGC cautioned against transitioning older adults to longer-acting BZDs prior to tapering.”
- Authors
- McLachlan, A. J., & Pont, L. G.
- Affiliations
- The University of Sydney (AU)
- Venue
- The Journals of Gerontology Series A: Biological Sciences and Medical Sciences
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-08-10
- Volume
- 67A
- Issue
- 2
- Pages
- 175-180
- ISSN
- 1079-5006 (ISSN-L)
- 1758-535X
- OpenAlex
- W2117045056
- Cited by
- 172
- References
- 51
- Citations by year
- 2026: 11 · 2025: 21 · 2024: 10 · 2023: 9 · 2022: 15 · 2021: 14 · 2020: 12 · 2019: 11 · 2018: 13 · 2017: 12 · 2016: 12 · 2015: 7 · 2014: 10 · 2013: 9 · 2012: 5
- FWCI
- 1.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journals of Gerontology Series A (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Medical Research Council
- National Health and Medical Research Council (571054)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Keywords
- drug metabolism, older adults, hepatic clearance, drug-metabolizing enzymes, hepatic blood flow, comorbidities, frailty, polypharmacy, pharmacogenetics, pharmacokinetics, adverse drug reactions, systemic exposure
- MeSH terms
- Aged, Aging, Pharmaceutical Preparations, Humans, Liver, Tissue Distribution
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