Enantioselective Analysis of Metoprolol in Plasma of Hypertensive Patients Undergoing Long-Term Therapy: Insights for Personalized Medicine Publisher



Seyfinejad B ; Jouyban K ; Houshyar J ; Sarmadian AJ ; Jouyban A
Source: BioImpacts Published:2025

Abstract

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. © 2025 The Author(s). This work is published by BioImpacts as an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/). Non-commercial uses of the work are permitted, provided the original work is properly cited.