Methadone--metabolism, pharmacokinetics and interactions.

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Ferrari A, Coccia CP, Bertolini A, Sternieri E

Methadone--metabolism, pharmacokinetics and interactions.

Pharmacol Res. 2004 Dec;50(6):551-9. doi: 10.1016/j.phrs.2004.05.002.

PubMed ID

15501692 [ View in PubMed

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Abstract

The pharmacokinetics of methadone varies greatly from person to person; so, after the administration of the same dose, considerably different concentrations are obtained in different subjects, and the pharmacological effect may be too small in some patients, too strong and prolonged in others. Methadone is mostly metabolised in the liver; the main step consists in the N-demethylation by CYP3A4 to EDDP (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine), an inactive metabolite. The activity of CYP3A4 varies considerably among individuals, and such variability is the responsible for the large differences in methadone bioavailability. CYP2D6 and probably CYP1A2 are also involved in methadone metabolism. During maintenance treatment with methadone, treatment with other drugs may be necessary due to the frequent comorbidity of drug addicts: psychotropic drugs, antibiotics, anticonvulsants and antiretroviral drugs, which can cause pharmacokinetic interactions. In particular, antiretrovirals, which are CYP3A4 inducers, can decrease the levels of methadone, so causing withdrawal symptoms. Buprenorphine, too, is metabolised by CYP3A4, and may undergo the same interactions as methadone. Since it is impossible to foresee the time-lapse from the administration of another drug to the appearing of withdrawal symptoms, nor how much the daily dose of methadone should be increased in order to prevent them, patients taking combined drug treatments must be carefully monitored. The so far known pharmacokinetic drug-drug interactions of methadone do not have life-threatening consequences for the patients, but they usually cause a decrease of the concentrations and of the effects of the drug, which in turn can cause symptoms of withdrawal and increase the risk of relapse into heroin abuse.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Methadone	Cytochrome P450 1A2	Protein	Humans	Unknown	Substrate	Details

Drug Interactions

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drugs	Interaction
Integrate drug-drug interactions in your software
Methadone Carbamazepine	The metabolism of Methadone can be increased when combined with Carbamazepine.
Methadone Aminoglutethimide	The serum concentration of Methadone can be increased when it is combined with Aminoglutethimide.
Methadone Testolactone	The serum concentration of Methadone can be increased when it is combined with Testolactone.
Methadone Exemestane	The serum concentration of Methadone can be increased when it is combined with Exemestane.
Methadone Letrozole	The serum concentration of Methadone can be increased when it is combined with Letrozole.