Physiologically Based Pharmacokinetic Model for Older Adults and Its Application in
Geriatric Drug Research

Xinyi      Wu; Jie   En Valerie   Sia; Min      Hai; Xuan      Lai; Haiyan      Li; Cheng      Cui; Dongyang      Liu
doi:10.2174/1389200224666230509104404
Abstract

Drug-related adverse events are higher in older patients than in non-older patients, increasing the risk of medication and reducing compliance. Aging is accompanied by a decline in physiological functions and metabolic weakening. Most tissues and organs undergo anatomical and physiological changes that may affect the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of drugs. Clinical trials are the gold standard for selecting appropriate dosing regimens. However, older patients are generally underrepresented in clinical trials, resulting in a lack of evidence for establishing an optimal dosing regimen for older adults. The physiologically based pharmacokinetic (PBPK) model is an effective approach to quantitatively describe the absorption, distribution, metabolism, and excretion of drugs in older adults by integrating physiological parameters, drug physicochemical properties, and preclinical or clinical PK data. The PBPK model can simulate the PK/PD characteristics of clinical drugs in different scenarios, ultimately compensating for inadequate clinical trial data in older adults, and is recommended by the Food and Drug Administration for clinical pharmacology studies in older adults. This review describes the effects of physiological changes on the PK/PD process in older adults and summarises the research progress of PBPK models. Future developments of PBPK models are also discussed, together with the application of PBPK models in older adults, aiming to assist the development of clinical study strategies in older adults.
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DOI https://dx.doi.org/10.2174/1389200224666230509104404	Print ISSN 1389-2002
Publisher Name Bentham Science Publisher	Online ISSN 1875-5453
Current Drug Metabolism

Physiologically Based Pharmacokinetic Model for Older Adults and Its Application in Geriatric Drug Research

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