Personalized Geriatric Pharmacotherapy: Pharmacogenomics, Polypharmacy, and Age-Related Pharmacokinetic and Pharmacodynamic Changes
Year: 2026
Type: article
Abstract: Aging induces profound physiological changes that alter drug disposition and response, narrowing therapeutic windows and increasing susceptibility to adverse drug reactions (ADRs). This review synthesizes current evidence on age-related pharmacokinetic and pharmacodynamic changes, with a focus on pharmacogenomic determinants of drug response in older adults. Progressive decline in renal function and hepatic metabolic capacity and alterations in body composition collectively necessitate age-appropriate dose adjustments. Polypharmacy, prevalent in community-dwelling and hospitalized older adults, compounds these challenges through drug–drug and drug–drug–gene interactions. Pharmacogenomic testing—particularly for CYP2D6, CYP2C19, CYP2C9, and SLCO1B1—offers a promising strategy with which to personalize therapy, while deprescribing frameworks provide practical approaches to mitigating medication-related risks. This review provides a comprehensive framework for understanding the mechanistic basis of altered drug response in older adults and proposes actionable strategies for optimizing pharmacotherapy in this vulnerable population. Throughout, pharmacogenomic claims are graded across four levels: biological plausibility, measured pharmacokinetic effect, pharmacogenetic actionability, and demonstrated clinical utility. Furthermore, selected gene–drug examples are explicitly identified as either geriatric-specific evidence or extrapolations from general adult pharmacogenomics, clarifying which findings are truly modified by the aging process.
DOI: 10.3390/ijms27219948
Language: English
Subfield: Pharmacology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,499
OpenAlex ID: W7204807731