BioImpacts · Published 2025-11-30 · DOI 10.34172/bi.32645
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.
Abstract from DOAJ. Public domain (CC0 1.0).
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