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Exploring venlafaxine pharmacokinetic variability with a phenotyping approach, a multicentric french-swiss study (MARVEL study)
- Source :
- BMC Pharmacology and Toxicology, BMC Pharmacology and Toxicology, BioMed Central, 2017, 18 (1), pp.70. 〈10.1186/s40360-017-0173-2〉, BMC Pharmacology and Toxicology, BioMed Central, 2017, 18 (1), pp.70. ⟨10.1186/s40360-017-0173-2⟩, BMC pharmacology & toxicology, vol. 18, no. 1, pp. 70, BMC Pharmacology & Toxicology, BMC Pharmacology and Toxicology, 2017, 18 (1), pp.70. ⟨10.1186/s40360-017-0173-2⟩, BMC Pharmacology & Toxicology, Vol. 18, No 1 (2017) P. 70, BMC Pharmacology and Toxicology, Vol 18, Iss 1, Pp 1-12 (2017)
- Publication Year :
- 2017
- Publisher :
- HAL CCSD, 2017.
-
Abstract
- It is well known that the standard doses of a given drug may not have equivalent effects in all patients. To date, the management of depression remains mainly empirical and often poorly evaluated. The development of a personalized medicine in psychiatry may reduce treatment failure, intolerance or resistance, and hence the burden and costs of mood depressive disorders. The Geneva Cocktail Phenotypic approach presents several advantages including the “in vivo” measure of different cytochromes and transporter P-gp activities, their simultaneous determination in a single test, avoiding the influence of variability over time on phenotyping results, the administration of low dose substrates, a limited sampling strategy with an analytical method developed on DBS analysis. The goal of this project is to explore the relationship between the activity of drug-metabolizing enzymes (DME), assessed by a phenotypic approach, and the concentrations of Venlafaxine (VLX) + O-demethyl-venlafaxine (ODV), the efficacy and tolerance of VLX. This study is a multicentre prospective non-randomized open trial. Eligible patients present a major depressive episode, MADRS over or equal to 20, treatment with VLX regardless of the dose during at least 4 weeks. The Phenotype Visit includes VLX and ODV concentration measurement. Following the oral absorption of low doses of omeprazole, midazolam, dextromethorphan, and fexofenadine, drug metabolizing enzymes activity is assessed by specific metabolite/probe concentration ratios from a sample taken 2 h after cocktail administration for CYP2C19, CYP3A4, CYP2D6; and by the determination of the limited area under the curve from the capillary blood samples taken 2–3 and 6 h after cocktail administration for CYP2C19 and P-gp. Two follow-up visits will take place between 25 and 40 days and 50–70 days after inclusion. They include assessment of efficacy, tolerance and observance. Eleven french centres are involved in recruitment, expected to be completed within approximately 2 years with 205 patients. Metabolic ratios are determined in Geneva, Switzerland. By showing an association between drug metabolism and VLX concentrations, efficacy and tolerance, there is a hope that testing drug metabolism pathways with a phenotypical approach would help physicians in selecting and dosing antidepressants. The MARVEL study will provide an important contribution to increasing the knowledge of VLX variability and in optimizing the use of methods of personalized therapy in psychiatric settings. ClinicalTrials.gov NCT02590185 (10/27/2015). This study is currently recruiting participants.
- Subjects :
- Male
Oncology
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
[SDV.NEU.PC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior
Venlafaxine
Pharmacology
030226 pharmacology & pharmacy
ATP-Binding Cassette, Sub-Family B, Member 1/metabolism
Adolescent
Adult
Aged
Aged, 80 and over
Antidepressive Agents, Second-Generation/blood
Antidepressive Agents, Second-Generation/pharmacokinetics
Antidepressive Agents, Second-Generation/therapeutic use
Cytochrome P-450 CYP2C19/metabolism
Cytochrome P-450 CYP2D6/metabolism
Cytochrome P-450 CYP3A/metabolism
Depressive Disorder, Major/drug therapy
Depressive Disorder, Major/metabolism
Female
France
Genotype
Humans
Middle Aged
Phenotype
Switzerland
Treatment Outcome
Venlafaxine Hydrochloride/blood
Venlafaxine Hydrochloride/pharmacokinetics
Venlafaxine Hydrochloride/therapeutic use
Young Adult
Study Protocol
[ SDV.NEU.SC ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences
0302 clinical medicine
80 and over
Cytochrome P-450 CYP3A
Medicine
Pharmacology (medical)
Major depressive episode
ComputingMilieux_MISCELLANEOUS
ddc:615
ddc:617
[SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior
Venlafaxine Hydrochloride
Area under the curve
[SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences
Antidepressive Agents
3. Good health
Cytochrome P-450 CYP2D6
[ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
[ SCCO.NEUR ] Cognitive science/Neuroscience
Antidepressive Agents, Second-Generation
medicine.symptom
medicine.drug
CYP2D6
medicine.medical_specialty
Major/drug therapy/metabolism
CYP2C19
[ SDV.NEU.PC ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior
03 medical and health sciences
Pharmacokinetics
lcsh:RA1190-1270
Internal medicine
Member 1/metabolism
ATP Binding Cassette Transporter, Subfamily B, Member 1
Dosing
lcsh:Toxicology. Poisons
Second-Generation/blood/pharmacokinetics/therapeutic use
Depressive Disorder
Depressive Disorder, Major
Sub-Family B
business.industry
[SCCO.NEUR]Cognitive science/Neuroscience
lcsh:RM1-950
[SCCO.NEUR] Cognitive science/Neuroscience
[SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
Cytochrome P-450 CYP2C19
lcsh:Therapeutics. Pharmacology
Venlafaxine Hydrochloride/blood/pharmacokinetics/therapeutic use
ATP-Binding Cassette
Personalized medicine
business
[SDV.NEU.SC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 20506511
- Database :
- OpenAIRE
- Journal :
- BMC Pharmacology and Toxicology, BMC Pharmacology and Toxicology, BioMed Central, 2017, 18 (1), pp.70. 〈10.1186/s40360-017-0173-2〉, BMC Pharmacology and Toxicology, BioMed Central, 2017, 18 (1), pp.70. ⟨10.1186/s40360-017-0173-2⟩, BMC pharmacology & toxicology, vol. 18, no. 1, pp. 70, BMC Pharmacology & Toxicology, BMC Pharmacology and Toxicology, 2017, 18 (1), pp.70. ⟨10.1186/s40360-017-0173-2⟩, BMC Pharmacology & Toxicology, Vol. 18, No 1 (2017) P. 70, BMC Pharmacology and Toxicology, Vol 18, Iss 1, Pp 1-12 (2017)
- Accession number :
- edsair.doi.dedup.....107970c21bb9dcf662f78228c039a98d