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Journal Articles BMC Pharmacology and Toxicology Year : 2017

Exploring venlafaxine pharmacokinetic variability with a phenotyping approach, a multicentric french-swiss study (MARVEL study)

1 OPTeN (UMR_S_1144 / U1144) - Optimisation thérapeutique en Neuropsychopharmacologie
2 Hôpital Lariboisière-Fernand-Widal [APHP]
3 HUG - Geneva University Hospital
4 SBIM - Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA)
5 Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]
6 CHU Montpellier
7 APHM - Assistance Publique - Hôpitaux de Marseille
8 CHU Clermont-Ferrand
9 NPsy-Sydo - Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux
10 Clinique Psychiatrique Universitaire [Tours]
11 CIC - Centre d’Investigation Clinique [Tours] CIC 1415
12 iBrain - Inserm U1253 - UNIV Tours - Imagerie et cerveau
13 CRNL - Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center
14 ULaval - Université Laval [Québec]
15 CHU - Centre Hospitalier Universitaire [Grenoble]
16 CIC Grenoble - Centre d'Investigation Clinique [Grenoble]
17 Service de psychiatrie
18 Fondation FondaMental [Créteil]
19 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
20 ToNIC - Toulouse Neuro Imaging Center
21 CIC 1436 - Centre d'investigation clinique de Toulouse
22 CIC Henri Mondor - Centre d'Investigation Clinique Henri Mondor
23 CHU Bordeaux [Bordeaux]
24 University of Bristol [Bristol]
25 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon
26 Lausanne University Hospital
27 CAPS - Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093]
28 IMRB - Institut Mondor de Recherche Biomédicale
Fanny Molière
  • Function : Author
Philippe Courtet
Florence Galtier

Abstract

Background: 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. Methods/design: 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.
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hal-01696753 , version 1 (02-04-2021)

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Célia Lloret-Linares, Youssef Daali, Sylvie Chevret, Isabelle Nieto, Fanny Molière, et al.. Exploring venlafaxine pharmacokinetic variability with a phenotyping approach, a multicentric french-swiss study (MARVEL study). BMC Pharmacology and Toxicology, 2017, 18 (1), pp.70. ⟨10.1186/s40360-017-0173-2⟩. ⟨hal-01696753⟩
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