Methadone Metabolism and Drug-Drug Interactions: In Vitro and In Vivo Literature Review.

Article Details

Citation

Volpe DA, Xu Y, Sahajwalla CG, Younis IR, Patel V

Methadone Metabolism and Drug-Drug Interactions: In Vitro and In Vivo Literature Review.

J Pharm Sci. 2018 Dec;107(12):2983-2991. doi: 10.1016/j.xphs.2018.08.025. Epub 2018 Sep 8.

PubMed ID
30205091 [ View in PubMed
]
Abstract

Methadone is utilized for the treatment of individuals with opiate dependence. Methadone undergoes N-demethylation by multiple cytochrome P450 (CYP) enzymes including CYP3A4, CYP2B6, CYP2C19, CYP2D6, CYP2C9, and CYP2C8. In vivo, polymorphism effects on methadone systemic exposure have been noted for CYP2B6, CYP3A4, and CYP2D6. Clinical drug interaction studies with antiviral drugs in methadone maintenance treatment patients yield varying results on methadone pharmacokinetics and pharmacodynamics. In general, CYP inhibitors altered methadone exposure with no adverse effects. CYP inducers generally decreased methadone exposure with some reports of withdrawal symptoms in the subjects. Interaction studies with antiviral drug combinations yielding differing results depend on the enzyme(s) affected. For certain antiviral medicines which are dual inhibitor(s) and inducer(s) for CYP enzymes, their effect on methadone pharmacokinetics can change with time since the effect of induction is usually delayed compared to the effect of inhibition.

DrugBank Data that Cites this Article

Drugs
Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
MethadoneCytochrome P450 2B6ProteinHumans
Unknown
Substrate
Inducer
Details
MethadoneCytochrome P450 2C18ProteinHumans
Unknown
Substrate
Details
MethadoneCytochrome P450 2C19ProteinHumans
Unknown
Substrate
Details
MethadoneCytochrome P450 2C8ProteinHumans
Unknown
Substrate
Details
MethadoneCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
MethadoneCytochrome P450 2D6ProteinHumans
No
Substrate
Inhibitor
Details
MethadoneCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Inhibitor
Inducer
Details
MethadoneCytochrome P450 3A7ProteinHumans
Unknown
Substrate
Details
Drug Carriers
DrugCarrierKindOrganismPharmacological ActionActions
MethadoneAlpha-1-acid glycoprotein 1ProteinHumans
No
Not AvailableDetails
MethadoneSerum albuminProteinHumans
No
Not AvailableDetails
Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
MethadoneP-glycoprotein 1ProteinHumans
Unknown
Inhibitor
Details
Drug Reactions
Reaction
Details