A Novel Framework for Assessing and Quantifying Drug Interaction Risk in Multimorbid Elderly Patients Receiving Polypharmacy in South West Nigeria

Quantifying drug interaction risk in multimorbid elderly patients receiving polypharmacy requires a framework that moves beyond pairwise interaction databases to account for pharmacokinetic and pharmacodynamic interaction synergism, patient vulnerability, and cumulative interaction burden. This study developed a novel framework for comprehensively assessing and quantifying drug interaction risk in this population at geriatric clinics in Lagos and Osun States. A multi-phase methodology was employed, comprising systematic literature synthesis of drug interaction assessment methodologies, prospective pharmacokinetic and pharmacodynamic monitoring in 80 elderly multimorbid patients (mean 8.3 medications per patient), and computational modelling to develop the quantification algorithm. Each patient's full medication list was assessed for pair-wise and higher-order interactions using mechanistic pharmacokinetic and pharmacodynamic modelling. Pharmacokinetic interactions were modelled using inhibitor/inducer competitive binding algorithms. Pharmacodynamic synergy was quantified using the Loewe additivity and Bliss independence models. An original Drug Interaction Risk Score (DIRS) aggregating individual interaction magnitudes, patient vulnerability indices (renal function, age, comorbidity score), and medication count was developed and calibrated against clinical outcome data. Higher DIRS scores were significantly associated with adverse drug events (OR 4.8 per 10-unit DIRS increase; p < 0.001), hospital admissions, and falls. The DIRS framework constitutes an original pharmacological contribution to drug interaction risk quantification and provides the theoretical basis for a clinical decision support tool for elderly patient prescribing in Nigeria. Keywords: drug interaction risk, polypharmacy, elderly patients, multimorbidity, novel risk scoring framework