Caroline Victorri-Vigneau1,2,3, Céline Verstuyft1,4, Régis Bouquié3, Edouard-Jules Laforgue2,3,5, Jean-Benoit Hardouin2, Juliette Leboucher5, Bertrand Le Geay6, Corine Dano7, Gaëlle Challet-Bouju2,5, Marie Grall-Bronnec2,5. 1. INSERM UMR_S1178, Team "Depression and Antidepressants", Medicine Faculty, CESP, Paris-Sud University, Le Kremlin Bicêtre, France. 2. INSERM UMR 1246, SPHERE, Methods in Patient-Centered Outcomes and Health Research, Nantes and Tours University, Nantes and Tours, France. 3. Clinical Pharmacology Department, CHU Nantes, Nantes, France. 4. Molecular Genetics, Pharmacogenetics and Hormonology Departments, Bicêtre Hospital, Group Paris-Sud, AP-HP, Le Kremlin Bicêtre, France. 5. Addictology and Psychiatry Department, CHU Nantes, Nantes, France. 6. Departement of Prison Psychiatry, CHU Nantes, Nantes, France. 7. Addictology department, CHU Angers, Angers, France.
Abstract
AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSION: The genotyping of CYP2B6 G516T could be an interesting tool to explore methadone intervariability.
AIMS: 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. METHODS: 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 methadonepatients was genotyped. RESULTS: 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). CONCLUSION: The genotyping of CYP2B6G516T could be an interesting tool to explore methadone intervariability.
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