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

British journal of clinical pharmacology 2019 Jul

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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. © 2019 The British Pharmacological Society.

Citation

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. Relevance of CYP2B6 and CYP2D6 genotypes to methadone pharmacokinetics and response in the OPAL study. British journal of clinical pharmacology. 2019 Jul;85(7):1538-1543