Current Concepts in Methadone Metabolism and Transport.
Article Details
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Kharasch ED
Current Concepts in Methadone Metabolism and Transport.
Clin Pharmacol Drug Dev. 2017 Mar;6(2):125-134. doi: 10.1002/cpdd.326.
- PubMed ID
- 28263461 [ View in PubMed]
- Abstract
Methadone is a cornerstone therapy for opioid addiction and a public health strategy for HIV/AIDS and hepatitis C reduction. Methadone is also used for acute and chronic pain. As use for chronic pain has grown, so too have adverse events. Constitutive and acquired (drug interactions) inter- and intraindividual variability in methadone pharmacokinetics and pharmacodynamics confounds reliable clinical use. Identification of enzymes and transporters responsible for methadone disposition has been a long-sought ideal. Initial in vitro studies identified CYP3A4 as metabolizing methadone. Subsequently, by extrapolation, CYP3A4 was long assumed to be responsible for clinical methadone disposition. However, CYP2B6 is also a major catalyst of methadone metabolism in vitro. It has now been unequivocally established that CYP2B6, not CYP3A4, is the principal determinant of methadone metabolism, clearance, elimination, and plasma concentrations in humans. Methadone disposition is susceptible to inductive and inhibitory drug interactions. CYP2B6 genetics also influences methadone metabolism and clearance, which were diminished in CYP2B6*6 carriers and increased in CYP2B6*4 carriers. CYP2B6 genetics can explain, in part, interindividual variability in methadone metabolism and clearance. Thus, both constitutive variability due to CYP2B6 genetics, and CYP2B6-mediated drug interactions, can alter methadone disposition, clinical effect, and drug safety. Methadone is not a substrate for major influx or efflux transporters.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Methadone Cytochrome P450 2C8 Protein Humans UnknownSubstrateDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareMethadoneVoriconazole The serum concentration of Methadone can be increased when it is combined with Voriconazole.