Addiction Biology · 2010 · 60 citations · 13 references
MedicinePharmacokineticsPharmacologyPharmacogeneticsPharmacogenomicsSubstance Use DisordersDrug DispositionDrug Metabolism GeneticsDrug Metabolism GenomicsGene - Drug InteractionsPharmacogenetic EpidemiologyPharmacogenomic Data InterpretationDrug Metabolism PolymorphismsInduction PhaseMedication-related DeathsMetabolizer Phenotype PredictionMethadone Maintenance TreatmentMethadone ToxicologySerious Adverse Drug ReactionsSerious Adverse Events
The largest proportion of methadone-associated deaths occurs during the drug induction phase. We analysed methadone-related fatalities for gene variations linked with methadone action. A significant association between high methadone concentrations and the CYP2B6*6 allele characteristic of the slow metabolizer phenotype was identified. We suggest that the risk of methadone fatality may be predetermined in part by the CYP2B6*6 allele. A significant correlation was also observed between post-mortem benzodiazepine concentrations and the OPRM1 A118G allele GA in methadone-related fatalities. Screening for these susceptibility variations prior to methadone prescription could assist in reducing the potential for serious adverse effects.
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Cherie E. Bond, K. Steven LaForge, Mingting Tian et al. · Proceedings of the National Academy of Sciences · 1998 · 1.1K citations