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

Sarah N Hilmer; Carl M J Kirkpatrick

doi:10.1093/ageing/afab003

journal article Mar 04, 2021

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

Sarah N Hilmer

Carl M J Kirkpatrick

Age and Ageing Vol. 50 No. 4 pp. 1054-1063 · Oxford University Press (OUP)

View at Publisher Save 10.1093/ageing/afab003

Abstract

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.

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References

Details

Published: Mar 04, 2021
Vol/Issue: 50(4)
Pages: 1054-1063
License: View

Authors

S

Sarah N Hilmer

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

C

Carl M J Kirkpatrick

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

Cite This Article

Sarah N Hilmer, Carl M J Kirkpatrick (2021). New Horizons in the impact of frailty on pharmacokinetics: latest developments. Age and Ageing, 50(4), 1054-1063. https://doi.org/10.1093/ageing/afab003

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

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