Relevance of CYP2B6 and CYP2D6 genotypes to methadone pharmacokinetics and response in the OPAL study.


Journal

British journal of clinical pharmacology
ISSN: 1365-2125
Titre abrégé: Br J Clin Pharmacol
Pays: England
ID NLM: 7503323

Informations de publication

Date de publication:
07 2019
Historique:
received: 25 09 2018
revised: 07 03 2019
accepted: 17 03 2019
pubmed: 26 3 2019
medline: 3 7 2020
entrez: 26 3 2019
Statut: ppublish

Résumé

Our study aimed to evaluate the impacts of the cytochrome P450 (CYP) 2B6-G516T and CYP2D6 genetic polymorphisms on pharmacokinetic and clinical parameters in patients receiving methadone maintenance treatment. Opioid PhArmacoLogy (OPAL) was a clinical survey of the sociodemographic characteristics, history and consequences of pathology associated with methadone maintenance treatment response and current addictive comorbidities. A subgroup of 72 methadone patients was genotyped. When comparing the three CYP2B6 genotype groups, the methadone (R)- and (S)-methadone enantiomer concentrations/doses (concentrations relative to doses) were different (P = .029, P = .0019). The CYP2D6 phenotypes did not seem to be relevant with regard to methadone levels. On multivariate analysis, neither the CYP2B6 genotype nor the CYP2D6 phenotype explained the (R)-methadone concentration/dose values (P = .92; P = .86); the (S)-methadone concentration/dose values (P = .052; P = .95 [although there was a difference between the TT group and GT and GG groups {P = .019}]); or opiate cessation (P = .12; P = .90). The genotyping of CYP2B6 G516T could be an interesting tool to explore methadone intervariability.

Identifiants

pubmed: 30907440
doi: 10.1111/bcp.13936
pmc: PMC6595468
doi:

Substances chimiques

CYP2B6 protein, human EC 1.14.14.1
Cytochrome P-450 CYP2B6 EC 1.14.14.1
Cytochrome P-450 CYP2D6 EC 1.14.14.1
Methadone UC6VBE7V1Z

Types de publication

Journal Article Multicenter Study Observational Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1538-1543

Informations de copyright

© 2019 The British Pharmacological Society.

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Auteurs

Caroline Victorri-Vigneau (C)

INSERM UMR_S1178, Team "Depression and Antidepressants", Medicine Faculty, CESP, Paris-Sud University, Le Kremlin Bicêtre, France.
INSERM UMR 1246, SPHERE, Methods in Patient-Centered Outcomes and Health Research, Nantes and Tours University, Nantes and Tours, France.
Clinical Pharmacology Department, CHU Nantes, Nantes, France.

Céline Verstuyft (C)

INSERM UMR_S1178, Team "Depression and Antidepressants", Medicine Faculty, CESP, Paris-Sud University, Le Kremlin Bicêtre, France.
Molecular Genetics, Pharmacogenetics and Hormonology Departments, Bicêtre Hospital, Group Paris-Sud, AP-HP, Le Kremlin Bicêtre, France.

Régis Bouquié (R)

Clinical Pharmacology Department, CHU Nantes, Nantes, France.

Edouard-Jules Laforgue (EJ)

INSERM UMR 1246, SPHERE, Methods in Patient-Centered Outcomes and Health Research, Nantes and Tours University, Nantes and Tours, France.
Clinical Pharmacology Department, CHU Nantes, Nantes, France.
Addictology and Psychiatry Department, CHU Nantes, Nantes, France.

Jean-Benoit Hardouin (JB)

INSERM UMR 1246, SPHERE, Methods in Patient-Centered Outcomes and Health Research, Nantes and Tours University, Nantes and Tours, France.

Juliette Leboucher (J)

Addictology and Psychiatry Department, CHU Nantes, Nantes, France.

Bertrand Le Geay (B)

Departement of Prison Psychiatry, CHU Nantes, Nantes, France.

Corine Dano (C)

Addictology department, CHU Angers, Angers, France.

Gaëlle Challet-Bouju (G)

INSERM UMR 1246, SPHERE, Methods in Patient-Centered Outcomes and Health Research, Nantes and Tours University, Nantes and Tours, France.
Addictology and Psychiatry Department, CHU Nantes, Nantes, France.

Marie Grall-Bronnec (M)

INSERM UMR 1246, SPHERE, Methods in Patient-Centered Outcomes and Health Research, Nantes and Tours University, Nantes and Tours, France.
Addictology and Psychiatry Department, CHU Nantes, Nantes, France.

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