Trial reportCPT: pharmacometrics & systems pharmacology2020
Examination of Metoprolol Pharmacokinetics and Pharmacodynamics Across CYP2D6 Genotype-Derived Activity Scores.
Trial report in CPT: pharmacometrics & systems pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2D6, ADRB1, ADRB2, ADRA2C, GRK4, and GRK5 Genotypes and Beta-Blocker Therapy.Clinical pharmacology and therapeutics · 2024Guideline
- Pharmacogenomics and chronotherapy of drug-induced cardioprotection in acute myocardial infarction.Nature communications · 2025Trial
- Population Pharmacokinetic Quantification of CYP2D6 Activity in Codeine Metabolism in Ambulatory Surgical Patients for Model-Informed Precision Dosing.Clinical pharmacokinetics · 2024Trial
- A randomized, cross-over trial of metoprolol succinate formulations to evaluate PK and PD end points for therapeutic equivalence.Clinical and translational science · 2022Trial
- CYP2D6 Metabolizer Status and Mortality in Metoprolol Users.Clinical and translational science · 2026Article
- Elucidating CYP2D6-driven metabolism and hepatotoxic bioactivation of metoprolol in plateable human and animal hepatocytes.ADMET & DMPK · 2025Article
- Distribution of Cytochrome P450 2D6 (*4, *9, *10, *41) alleles in healthy population from north-west of Iran.ARYA atherosclerosis · 2025Article
- Impact of CYP2D6*2, CYP2D6*35, rs5758550, and related haplotypes on risperidone clearance in vivo.European journal of clinical pharmacology · 2024Article
- Metoprolol andJournal of personalized medicine · 2023Article
- A frequent CYP2D6 variant promotes skipping of exon 3 and reduces CYP2D6 protein expression in human liver samples.Frontiers in pharmacology · 2023Article
- Implementing a pragmatic clinical trial to tailor opioids for acute pain on behalf of the IGNITE ADOPT PGx investigators.Clinical and translational science · 2022Article
- Nonadherence by Serum Drug Analyses in Resistant Hypertension: 7-Year Follow-Up of Patients Considered Adherent by Directly Observed Therapy.Journal of the American Heart Association · 2022Article
- Physiologically-based pharmacokinetic modeling of dextromethorphan to investigate interindividual variability within CYP2D6 activity score groups.CPT: pharmacometrics & systems pharmacology · 2022Article
- The Impact of the CYP2D6 "Enhancer" Single Nucleotide Polymorphism on CYP2D6 Activity.Clinical pharmacology and therapeutics · 2022Article
- Pharmacogenomics of Hypertension in CKD: The CKD-PGX Study.Kidney360 · 2022Article
- Physiologically Based Pharmacokinetic Modeling of Metoprolol Enantiomers and α-Hydroxymetoprolol to Describe CYP2D6 Drug-Gene Interactions.Pharmaceutics · 2020Article
Corrections and comments
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Authors and funding
25 authors.
Funding
Abstract
Recent CYP2D6 phenotype standardization efforts by CYP2D6 activity score (AS) are based on limited pharmacokinetic (PK) and pharmacodynamic (PD) data. Using data from two independent clinical trials of metoprolol, we compared metoprolol PK and PD across CYP2D6 AS with the goal of determining whether the PK and PD data support the new phenotype classification. S-metoprolol apparent oral clearance (CLo), adjusted for clinical factors, was correlated with CYP2D6 AS (P < 0.001). The natural log of CLo was lower with an AS of 1 (7.6 ± 0.4 mL/minute) vs. 2-2.25 (8.3 ± 0.6 mL/minute; P = 0.012), similar between an AS of 1 and 1.25-1.5 (7.8 ± 0.5 mL/minute; P = 0.702), and lower with an AS of 1.25-1.5 vs. 2-2.25 (P = 0.03). There was also a greater reduction in heart rate with metoprolol among study participants with AS of 1 (-10.8 ± 5.5) vs. 2-2.25 (-7.1 ± 5.6; P < 0.001) and no significant difference between those with an AS of 1 and 1.25-1.5 (-9.2 ± 4.7; P = 0.095). These data highlight linear trends among CYP2D6 AS and metoprolol PK and PD, but inconsistencies with the phenotypes assigned by AS based on the current standards. Overall, this case study with metoprolol suggests that utilizing CYP2D6 AS, instead of collapsing AS into phenotype categories, may be the most precise approach for utilizing CYP2D6 pharmacogenomics in clinical practice.
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