Behrouz Seyfinejad
1,2 
, Kimiya Jouyban
3 , Jalil Houshyar
4, Amirreza Jabbaripour Sarmadian
5, Abolghasem Jouyban
2,6* 1 Cellular and Molecular Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran
2 Pharmaceutical Analysis Research Center, Pharmaceutical Sciences Institute, Tabriz University of Medical Sciences, Tabriz, Iran
3 Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
4 Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
5 Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
6 Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
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.