Pharmacokinetic Modeling of Drug Absorption in Elderly using a Two-Compartment Algorithm

Abstract

Physiological changes with age profoundly affect drug absorption, distribution, metabolism, and excretion 
in the elderly population. This paper describes a pharmacokinetic model based on a two-compartment 
algorithm for defining the drug absorption kinetics in older people. The model encompasses key variables 
associated with aging, including diminished gastrointestinal motility, altered plasma protein binding, and 
reduced hepatic and renal clearance. Parameters were fit on clinical pharmacokinetic information for 
geriatric drugs of frequent prescription. The two-compartment model accurately mimics the central and 
peripheral distribution of the drug, enabling a precise study of the absorption phase and systemic 
availability. Simulation by the model indicates a delayed time to absorption and a delay in peak plasma 
concentration in the elderly population compared with young subjects. Sensitivity analysis confirms that 
even minimal variations in the rate constants of absorption or clearance values may considerably influence 
therapeutic performance. These results emphasize the importance of adjusting doses by age and advocate 
the use of compartmental models to improve the design of more effective and safer pharmacotherapy for 
the elderly. The model is a valuable tool for geriatric drug discovery and clinical optimal dosing.