Very strong correlations of metoprolol- and solanidine-derived metabolic ratios in a real-world cohort with a stable metoprolol drug regimen

Q: What are the key findings of this study?

Solanidine-derived metabolic ratios correlated very strongly (r = 0.907) with metoprolol metabolic ratios, serving as a stronger predictor of CYP2D6 activity than genotype-derived activity scores.

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Cardiovascular conditions requiring stable metoprolol therapy (n=48). Intervention: Solanidine-derived phenotyping vs. CYP2D6 genotyping. Primary outcome: Correlation of ln MR (OH-solanidine/solanidine) with ln MR (OH-metoprolol/metoprolol) (r = 0.907, 95% CI 0.838-0.948, p=<0.0001).

Q: What does this research mean for the field?

Solanidine-derived metabolic ratios correlate strongly with metoprolol metabolic ratios and predict CYP2D6 activity and metoprolol trough levels more accurately than genotype-derived activity scores. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To compare solanidine-derived phenotyping with genotyping-derived activity scores for predicting metoprolol metabolism in patients receiving a stable metoprolol regimen.

Jens Andreas Sarömba; Berkan Kurt; Alessandra Antwerpen; Karen Rex; Anna Giacin; Justus Bornemann; Kaan Aygar; Marieke Mertens; D Müller-Wieland; Edgar Dahl; Nikolaus Marx; Florian Kahles; Justyna Wozniak; Jule Neiß; Dominik Krzoska; Julia Stingl; Julian Peter Müller; Katja S. Just

doi:10.3389/fphar.2026.1812007

May 29, 2026Frontiers in PharmacologyOpen Access

Very strong correlations of metoprolol- and solanidine-derived metabolic ratios in a real-world cohort with a stable metoprolol drug regimen

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Key result

Solanidine metabolic ratios show ~0.91 correlation with metoprolol metabolism, predicting CYP2D6 activity better than genotype scores.

r = 0.907
95% CI 0.838-0.948
P<0.0001
n=48

Figures

Why the study?

Does solanidine-derived phenotyping predict metoprolol metabolism better than genotyping in patients on a stable metoprolol regimen?

Key Points

To compare solanidine-derived phenotyping with genotyping-derived activity scores for predicting metoprolol metabolism in patients receiving a stable metoprolol regimen.
Assessed N = 48 patients from the ARIANA registry (DRKS00025716) on stable metoprolol therapy, screening medical records for CYP2D6-interfering medications.
Quantified fasting plasma concentrations of metoprolol, solanidine, and their metabolites using liquid chromatography-tandem mass spectrometry (LC-MS).
Conducted CYP2D6 genotyping using the Infinium Global Diversity Array with Enhanced PGx to calculate activity scores and evaluate metabolic ratios.
Among N = 47 analyzed patients, ln MR (OH-metoprolol/metoprolol) correlated strongly with ln MR (OH-solanidine/solanidine) (r = 0.907, 95% CI: 0.838–0.948, R2 = 0.823, p < 0.0001) and ln MR (SSDA/solanidine) (r = 0.946, 95% CI: 0.905–0.970, R2 = 0.896, p < 0.0001).
Solanidine metabolic ratios correlated negatively with metoprolol trough levels (r = -0.513, 95% CI: -0.698 to -0.265 and r = -0.533, 95% CI: -0.711 to -0.291), whereas genotype-derived activity scores showed weaker correlation (r = -0.288, 95% CI: -0.531 to -0.001, p = 0.499).
In multiple regression models adjusting for covariates, solanidine-derived metabolic ratios explained more variance in metoprolol concentrations (R2 = 0.614 and R2 = 0.599) than the genotype-predicted activity score (R2 = 0.386).

Study Design

Type

Cohort (n=48)

Multicenter

No

Structured PICO

Does solanidine-derived phenotyping predict metoprolol metabolism better than genotyping in patients on a stable metoprolol regimen?

P

Population

47 patients from the "All-comer" Registry for ImmunocArdiology aNd cardiometabolic disease Aachen (ARIANA) study with a stable metoprolol regimen and detectable metoprolol plasma concentrations.

I

Intervention

Solanidine-derived phenotyping (metabolic ratios of solanidine measured via LC-MS)

C

Comparator

Genotyping-derived CYP2D6 activity score (Infinium Global Diversity Array with Enhanced PGx)

O

Outcome

Correlation with metoprolol metabolic ratio (OH-metoprolol/metoprolol) and metoprolol trough levelssurrogate

Main Result

Effect estimate: r = 0.907 (95% CI 0.838-0.948)

p-value: p=<0.0001

Solanidine-derived phenotyping provides a more accurate prediction of CYP2D6 activity and metoprolol trough levels compared to standard genotyping.

Limitations

Small sample size
Unsupervised dosing of metoprolol
Genotyping method did not test for NFIB rs28379954 T>C polymorphism
Did not discern structural variants such as CYP2D6/CYP2D7 hybrid genes

Implication

Solanidine ratios may enhance CYP2D6 phenotyping accuracy over genotyping; leaves open prospective validation for metoprolol dosing.

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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Cite This Study

Sarömba et al. (2026) conducted a cohort in Cardiovascular conditions requiring stable metoprolol therapy (n=48). Solanidine-derived phenotyping vs. CYP2D6 genotyping was evaluated on Correlation of ln MR (OH-solanidine/solanidine) with ln MR (OH-metoprolol/metoprolol) (r = 0.907, 95% CI 0.838-0.948, p=<0.0001). Solanidine-derived metabolic ratios correlated very strongly (r = 0.907) with metoprolol metabolic ratios, serving as a stronger predictor of CYP2D6 activity than genotype-derived activity scores.

synapsesocial.com/papers/6a3c2384d15afadd906fa489 https://doi.org/10.3389/fphar.2026.1812007

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Very strong correlations of metoprolol- and solanidine-derived metabolic ratios in a real-world cohort with a stable metoprolol drug regimen

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Very strong correlations of metoprolol- and solanidine-derived metabolic ratios in a real-world cohort with a stable metoprolol drug regimen

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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