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

Article date: July 2019

By: Caroline Victorri‐Vigneau, Céline Verstuyft, Régis Bouquié, Edouard‐Jules Laforgue, Jean‐Benoit Hardouin, Juliette Leboucher, Bertrand Le Geay, Corine Dano, Gaëlle Challet‐Bouju, Marie Grall‐Bronnec in Volume 85, Issue 7, pages 1538-1543


Our study aimed to evaluate the impacts of the cytochrome P450 (CYP) 2B6G516T 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.

DOI: 10.1111/bcp.13936

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