ArticleFrontiers in pharmacology2026
Very strong correlations of metoprolol- and solanidine-derived metabolic ratios in a real-world cohort with a stable metoprolol drug regimen.
Article in Frontiers in pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: Individual CYP2D6 activity can be assessed with minimal invasiveness by genotyping and solanidine-derived phenotyping. In this study, we aimed to compare the two methods to predict the metabolism of the CYP2D6 substrate metoprolol in a cohort of the "All-comer" Registry for ImmunocArdiology aNd cardiometabolic disease Aachen (ARIANA) study (DRKS00025716; https://drks.de/search/de/trial/DRKS00025716) with a stable metoprolol regimen. Methods: In total, N = 48 patients were clinically assessed, and their medical records were analyzed for CYP2D6-interfering drugs. Plasma samples collected in a fasted state were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS). Genotyping was performed using the Infinium Global Diversity Array with Enhanced PGx. CYP2D6 activity scores and metabolic ratios (MRs) of solanidine and metoprolol were calculated. Results: N = 47 patients with detectable metoprolol plasma concentrations were included in the primary analysis. The MRs ln MR (OH-solanidine/solanidine) and ln MR (3,4-seco solanidine-3,4-dioic acid/solanidine) correlated very strongly (r = 0.907 and r = 0.945) with the ln MR (OH-metoprolol/metoprolol). There was a strong negative correlation of both solanidine-derived MRs with metoprolol trough levels (r = -0.625 and r = -0.703). The genotyping-derived CYP2D6 activity score showed weaker correlations in all comparisons, even when adjusting for covariates. Discussion: Solanidine-derived phenotyping showed stronger correlations to the measured CYP2D6 activity and metoprolol trough levels than the genotyping-derived activity scores. More research is needed in order to implement solanidine-derived dosing recommendations into clinical practice.
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