Methadone Metabolism and Drug-Drug Interactions: In Vitro and In Vivo Literature Review.
Article Details
- CitationCopy to clipboard
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
Drug Enzyme Kind Organism Pharmacological Action Actions Methadone Cytochrome P450 2B6 Protein Humans UnknownSubstrateInducerDetails Methadone Cytochrome P450 2C18 Protein Humans UnknownSubstrateDetails Methadone Cytochrome P450 2C19 Protein Humans UnknownSubstrateDetails Methadone Cytochrome P450 2C8 Protein Humans UnknownSubstrateDetails Methadone Cytochrome P450 2C9 Protein Humans UnknownSubstrateDetails Methadone Cytochrome P450 2D6 Protein Humans NoSubstrateInhibitorDetails Methadone Cytochrome P450 3A4 Protein Humans UnknownSubstrateInhibitorInducerDetails Methadone Cytochrome P450 3A7 Protein Humans UnknownSubstrateDetails - Drug Carriers
Drug Carrier Kind Organism Pharmacological Action Actions Methadone Alpha-1-acid glycoprotein 1 Protein Humans NoNot Available Details Methadone Serum albumin Protein Humans NoNot Available Details - Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Methadone P-glycoprotein 1 Protein Humans UnknownInhibitorDetails - Drug Reactions
Reaction Details