Enantioselective analysis of metoprolol in plasma of hypertensive patients undergoing long-term therapy: Insights for personalized medicine.

Introduction: Metoprolol is therapeutically formulated as a racemate with stereoselective pharmacokinetics influenced by CYP2D6 polymorphism. Understanding enantioselective disposition is critical for optimizing therapy in hypertensive patients, particularly during long-term treatment, where metabolic and excretory pathways may interact unpredictably. Methods: This study analyzed plasma samples from 18 hypertensive patients on long-term metoprolol therapy using a validated chiral capillary electrophoresis method. Enantiomer concentrations were quantified, and S/R ratios were evaluated alongside patient demographics, dosing regimens, and co-administered drugs. The study design focused on identifying deviations from expected enantiomeric patterns observed in single-dose or short-term multi-dose administration in healthy individuals studies. Results: While most patients (70%) exhibited the anticipated S/R ratio≥1, 30% demonstrated inverted plasma S/R ratios (<1), suggesting altered renal excretion or CYP2D6 saturation. Conclusion: Long-term metoprolol therapy reveals complex enantioselective disposition influenced by metabolic phenotype, renal excretion and drug interactions. The unexpected S/R inversion underscores the need for personalized dosing, particularly in patients with renal impairment or polypharmacy. Enantiomer monitoring may complement pharmacogenomic strategies to optimize therapeutic outcomes.