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Observational Study
. 2019 Jul;85(7):1538-1543.
doi: 10.1111/bcp.13936. Epub 2019 May 11.

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

Caroline Victorri-Vigneau  1   2   3 , Céline Verstuyft  1   4 , Régis Bouquié  3 , Edouard-Jules Laforgue  2   3   5 , Jean-Benoit Hardouin  2 , Juliette Leboucher  5 , Bertrand Le Geay  6 , Corine Dano  7 , Gaëlle Challet-Bouju  2   5 , Marie Grall-Bronnec  2   5
Affiliations
Observational Study

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

Caroline Victorri-Vigneau et al. Br J Clin Pharmacol. 2019 Jul.

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.

Keywords: CYP2B6; CYP2D6; methadone; pharmacokinetic; response to treatment.

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Conflict of interest statement

There are no competing interests to declare.

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