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Relevance of CYP2B6 and CYP2D6 genotypes to methadone pharmacokinetics and response in the OPAL study
Author(s) -
VictorriVigneau Caroline,
Verstuyft Céline,
Bouquié Régis,
Laforgue EdouardJules,
Hardouin JeanBenoit,
Leboucher Juliette,
Le Geay Bertrand,
Dano Corine,
ChalletBouju Gaëlle,
GrallBronnec Marie
Publication year - 2019
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.13936
Subject(s) - methadone , cyp2b6 , cyp2d6 , pharmacokinetics , medicine , genotype , pharmacology , pharmacogenetics , methadone maintenance , opioid , opiate substitution treatment , genotyping , dosing , anesthesia , cytochrome p450 , buprenorphine , biology , cyp3a4 , genetics , receptor , metabolism , gene
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.