Pharmacokinetic and pharmacodynamic alterations in older people: what we know so far

Healthcare professionals face increasing challenges when managing older patients, a group characterized by significant interindividual variability in comorbidity patterns, homeostatic capacity, frailty status, cognitive function, and life expectancy. Complex therapeutic decisions may increase the risk of inappropriate polypharmacy, drug-drug, and drug-disease interactions in the context of age-associated pharmacokinetic and pharmacodynamic alterations, with consequent drug accumulation and toxicity.

This state-of-the-art narrative review article summarizes and critically appraises the results of original research studies and reviews published in PubMed, Scopus, and Web of Science, from inception to 9 April 2025, on age-associated changes in critical organs and systems and relevant pharmacokinetic and pharmacodynamic alterations. It also discusses the emerging role of frailty and the gut microbiota in influencing such alterations and the potential utility of machine learning techniques in identifying new signals of drug efficacy and toxicity in older patients.

The available knowledge regarding specific age-associated pharmacokinetic and pharmacodynamic alterations applies to a limited number of drugs, some of which are not frequently prescribed in contemporary practice. Future studies investigating a wider range of drugs and their patterns of use will likely enhance therapeutic efficacy and minimize toxicity in the older patient population.