Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alleles*
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Aryl Hydrocarbon Hydroxylases / genetics*
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Benzodiazepines / pharmacokinetics
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Benzodiazepines / toxicity
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Cause of Death
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Cytochrome P-450 CYP2B6
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Drug Synergism
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Gene Frequency / genetics
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Genetic Carrier Screening
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Genetic Predisposition to Disease / genetics
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Genetic Testing
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Genetic Variation / genetics*
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Genotype*
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Heroin Dependence / blood
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Heroin Dependence / mortality*
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Heroin Dependence / rehabilitation*
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Humans
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Methadone / pharmacokinetics
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Methadone / toxicity*
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Morphine / pharmacokinetics
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Narcotics / pharmacokinetics
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Narcotics / toxicity*
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Opiate Substitution Treatment / adverse effects*
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Opiate Substitution Treatment / mortality*
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Oxidoreductases, N-Demethylating / genetics*
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Receptors, Opioid, mu / genetics*
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Risk Factors
Substances
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Narcotics
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OPRM1 protein, human
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Receptors, Opioid, mu
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Benzodiazepines
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Morphine
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Aryl Hydrocarbon Hydroxylases
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CYP2B6 protein, human
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Cytochrome P-450 CYP2B6
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Oxidoreductases, N-Demethylating
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Methadone