Trial reportPsychopharmacology2015
The influences of CYP2D6 genotypes and drug interactions on the pharmacokinetics of venlafaxine: exploring predictive biomarkers for treatment outcomes.
Trial report in Psychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 2 of them syntheses that pooled it.
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Who cites it
13 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction between CYP2D6, CYP2C19 and non-SSRI/non-TCA antidepressants.European journal of human genetics : EJHG · 2024Guideline
- Genetic endophenotypes for insomnia of major depressive disorder and treatment-induced insomnia.Journal of neural transmission (Vienna, Austria : 1996) · 2019Pooled it
- Pioneering a Hybrid Decentralized Clinical Trial in South Korea: Assessing Feasibility, Data Integrity, and Participant Perceptions.Clinical and translational science · 2026Trial
- Pharmacokinetic Drug-Drug Interactions of DA-8010 with Clarithromycin or Rifampicin: Influence of CYP2D6 Phenotype on the Extent of These Interactions.Drug design, development and therapy · 2026Trial
- Trial
- Exploratory Evaluation of Solanidine as an Endogenous Marker for CYP2D6-Mediated Drug-Drug-Gene Interactions of Venlafaxine in Koreans.Clinical and translational science · 2026Article
- Pharmacogenomic study-A pilot study of the effect of pharmacogenomic phenotypes on the adequate dosing of verapamil for migraine prevention.The pharmacogenomics journal · 2024Article
- Physiologically Based Pharmacokinetic Modeling to Unravel the Drug-gene Interactions of Venlafaxine: Based on Activity Score-dependent Metabolism by CYP2D6 and CYP2C19 Polymorphisms.Pharmaceutical research · 2024Article
- Serotonergic receptor gene polymorphism and response to selective serotonin reuptake inhibitors in ethnic Malay patients with first episode of major depressive disorder.The pharmacogenomics journal · 2021Review
- In Vitro and In Vivo Rat Model Assessments of the Effects of Vonoprazan on the Pharmacokinetics of Venlafaxine.Drug design, development and therapy · 2020Article
- Pharmacokinetic correlates of venlafaxine: associated adverse reactions.European archives of psychiatry and clinical neuroscience · 2019Article
- Pharmacokinetics of venlafaxine in treatment responders and non-responders: a retrospective analysis of a large naturalistic database.European journal of clinical pharmacology · 2019Article
- Prediction of Drug-Drug Interactions with Bupropion and Its Metabolites as CYP2D6 Inhibitors Using a Physiologically-Based Pharmacokinetic Model.Pharmaceutics · 2017Article
Corrections and comments
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
rationaleTwo biomarkers: concentration ratio of O-desmethylvenlafaxine/venlafaxine and concentration sum of venlafaxine + O-desmethylvenlafaxine were adopted to indicate venlafaxine responses, but neither is validated.
objectivesTo evaluate the ability of two biomarkers in reflecting venlafaxine pharmacokinetic variations, and to further examine their relationship with venlafaxine treatment outcomes.
methodsTwo well-defined influencing factors: CYP2D6 genotypes and drug interactions were enriched into a three-period crossover study to produce venlafaxine pharmacokinetic variations: In each period, healthy CYP2D6 extensive metabolizers (EM group; n = 12) and CYP2D6*10/*10 intermediate metabolizers (IM group; n = 12) were pretreated with clarithromycin (CYP3A4 inhibitor), or nothing (control), or clarithromycin + paroxetine (CYP3A4 + CYP2D6 inhibitors), before administration of a single-dose of 75 mg venlafaxine. Both biomarkers were evaluated (1) for their relationship with the influencing factors in healthy volunteers and (2) for their relationships with the venlafaxine responses/adverse events reported in two patient studies.
resultsSignificant venlafaxine pharmacokinetic variations were observed between the EM and IM groups (geometric mean ratio [95 % CI] of area under the curve, 3.0 [1.8-5.1] in the control period), and between the control and clarithromycin + paroxetine periods (4.1 [3.5-4.7] and 2.0 [1.7-2.4] in the EM and IM group, respectively). O-Desmethylvenlafaxine/venlafaxine was superior to venlafaxine + O-desmethylvenlafaxine to reflect the influencing factors. In the patient studies, O-desmethylvenlafaxine/venlafaxine > 4 showed high precision in predicting venlafaxine responders/partial-responders (92 %) and patients without venlafaxine-related adverse events (88 %); the O-desmethylvenlafaxine/venlafaxine < 4 and venlafaxine + O-desmethylvenlafaxine > 400 ng/ml combination showed higher precision (100 %) than O-desmethylvenlafaxine/venlafaxine < 4 alone (65 %) in predicting venlafaxine non-responders.
conclusionWe propose using O-desmethylvenlafaxine/venlafaxine for CYP2D6 phenotyping, and O-desmethylvenlafaxine/venlafaxine with venlafaxine + O-desmethylvenlafaxine for predicting venlafaxine treatment outcomes in future prospective studies.
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