ArticleBritish journal of clinical pharmacology2019
Significantly lower CYP2D6 metabolism measured as the O/N-desmethylvenlafaxine metabolic ratio in carriers of CYP2D6*41 versus CYP2D6*9 or CYP2D6*10: a study on therapeutic drug monitoring data from 1003 genotyped Scandinavian patients.
Article in British journal of clinical pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Cytochrome P450 2D6 genotype-phenotype characterization through population pharmacokinetic modeling of tedatioxetine.CPT: pharmacometrics & systems pharmacology · 2021Pooled it
- Venlafaxine reduces hot flashes in hormone receptor-positive breast cancer patients receiving tamoxifen: a prospective single-arm, open-label trial.Breast cancer (Tokyo, Japan) · 2026Trial
- Population Pharmacokinetic Quantification of CYP2D6 Activity in Codeine Metabolism in Ambulatory Surgical Patients for Model-Informed Precision Dosing.Clinical pharmacokinetics · 2024Trial
- Preliminary Evidence for Sex Differences in CYP2C19 Metabolic Capacity During Psychotropic Drug Treatment.Genes · 2026Article
- A consideration of CYP2D6 genetic variations in the Ghanaian population as a potential 'culprit' for the tramadol 'abuse crisis'.BMC medical genomics · 2024Article
- Case report: Avoiding intolerance to antipsychotics through a personalized treatment approach based on pharmacogenetics.Frontiers in psychiatry · 2024Article
- Estimating the In Vivo Function of CYP2D6 Alleles through Population Pharmacokinetic Modeling of Brexpiprazole.Clinical pharmacology and therapeutics · 2023Article
- Drug Metabolism: A Half-Century Plus of Progress, Continued Needs, and New Opportunities.Drug metabolism and disposition: the biological fate of chemicals · 2023Article
- Case report: application of pharmacogenetics in the personalized treatment of an elderly patient with a major depressive episode.Frontiers in psychiatry · 2023Article
- Current Status of Therapeutic Drug Monitoring in Mental Health Treatment: A Review.Pharmaceutics · 2022Review
- Pharmacogenomics in Psychiatry Practice: The Value and the Challenges.International journal of molecular sciences · 2022Review
- Relationships between CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 metabolic phenotypes and genotypes in a Nicaraguan Mestizo population.The pharmacogenomics journal · 2021Article
- Impairment of endoxifen formation in tamoxifen-treated premenopausal breast cancer patients carrying reduced-function CYP2D6 alleles.British journal of clinical pharmacology · 2021Article
- Quantification of In Vivo Metabolic Activity of CYP2D6 Genotypes and Alleles Through Population Pharmacokinetic Analysis of Vortioxetine.Clinical pharmacology and therapeutics · 2021Article
- Article
- Optimising Seniors' Metabolism of Medications and Avoiding Adverse Drug Events Using Data on How Metabolism by Their P450 Enzymes Varies with Ancestry and Drug-Drug and Drug-Drug-Gene Interactions.Journal of personalized medicine · 2020Article
- Prescribed Doses of CYP2D6-Metabolized Drugs and Hemodynamic Responses in Relation to CYP2D6 Genotype Among Older Patients Exposed to Polypharmacy.Drugs & aging · 2020Article
- Impact of genotype-predicted CYP2D6 metabolism on clinical effects and tolerability of metoprolol in patients after myocardial infarction - a prospective observational study.European journal of clinical pharmacology · 2020Observational
- Pharmacogenomics of Antidepressant and Antipsychotic Treatment: How Far Have We Got and Where Are We Going?Frontiers in psychiatry · 2020Review
- Impact of age and CYP2D6 genetics on exposure of aripiprazole and dehydroaripiprazole in patients using long-acting injectable versus oral formulation: relevance of poor and intermediate metabolizer status.European journal of clinical pharmacology · 2020Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsCYP2D6*9, CYP2D6*10 and CYP2D6*41 are the most frequent reduced-function CYP2D6 alleles in Caucasians. Despite lacking in vivo evidence, they are collectively classified with an enzyme activity score of 0.5. Thus, the aim of this study was to compare the functional impact of CYP2D6*9, CYP2D6*10 and CYP2D6*41 on CYP2D6 metabolism in a large patient population.
methodsA total of 1003 patients (mainly Caucasians) with data on CYP2D6 genotype and serum concentrations of venlafaxine and metabolites were included from a therapeutic drug monitoring service in Oslo, Norway. The O-desmethyl-to-N-desmethyl-venlafaxine metabolic ratio (MR) was applied as CYP2D6 biomarker and compared (Mann-Whitney) between carriers of CYP2D6*9-10 (merged) and CYP2D6*41, either combined with CYP2D6*1 or non-coding (null) alleles. MR subgroup estimates were obtained by multiple linear regression for calculations of CYP2D6*9-10 and CYP2D6*41 activity scores.
resultsMR was significantly lower in carriers of CYP2D6*41 than CYP2D6*9-10 (P < 0.002). The majority of CYP2D6*41/null carriers (86.7%) had MR in the observed range of CYP2D6null/null carriers compared with the minority of CYP2D6*9-10/null carriers (17.4%). CYP2D6 genotype explained 60.7% of MR variability in the multivariate analysis providing subgroup estimates of 9.54 (95% CI; 7.45-12.20), 3.55 (2.06-6.10), 1.33 (0.87-2.05) and 0.47 (0.35-0.61) in carriers of CYP2D6*1/null (n = 269), CYP2D6*9-10/null (n = 17), CYP2D6*41/null (n = 30) and CYP2D6null/null (n = 95), respectively. Based on these estimates, the calculated activity score of CYP2D6*41 was 0.095 compared to 0.34 for CYP2D6*9-10.
conclusionsCYP2D6 metabolism measured as the O/N-desmethylvenlafaxine ratio is significantly lower in Scandinavian carriers of CYP2D6*41 vs. CYP2D6*9-10. Thus, these alleles should be differentiated when classifying CYP2D6 phenotype from genotype.
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