Dosage Adjustment in Polypharmacy Management using Age Specific PK Simulation Algorithms
Keywords:
Polypharmacy, Geriatric Pharmacotherapy, Age-Specific Pharmacokinetics, Model-Informed Precision Dosing (MIPD), Pharmacokinetic Simulation, Dosage Optimization, Clinical Decision Support Systems.Abstract
Polypharmacy in older people is an important clinical issue with drug pharmacokinetic changes associated
with aging that enhance the risk of adverse drug effects and loss of therapeutic efficacy. In this hypothesis,
a model-informed precision dosing (MIPD) approach is assumed, utilizing age-scaled pharmacokinetic
(PK) simulation algorithms to personalize drug therapy in the management of polypharmacy. Clinical
information was collected from older people and used to estimate crucial PK parameters such as clearance
and volume of distribution. Simulations were run to predict patient-specific drug concentration-time
profiles for five drugs of frequent use. Dosage adjustment was then suggested based on simulated systemic
exposure (AUC and Cmax) and confirmed against the observed results. The outcomes showed that more
than 70% of the patients needed dose adjustment, especially for kidney-excreting or minimally clear drugs.
A large number of patients achieved therapeutic targets after adjustments with simulation, validating the
model's utility. These results promise well for future age-adjusted PK modeling to reduce drug toxicity and
maximize the safety and efficacy of treatment in multimorbid elderly patients.