Inhibition of human cytochrome P450 2D6 (CYP2D6) by methadone.

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Wu D, Otton SV, Sproule BA, Busto U, Inaba T, Kalow W, Sellers EM

Inhibition of human cytochrome P450 2D6 (CYP2D6) by methadone.

Br J Clin Pharmacol. 1993 Jan;35(1):30-4. doi: 10.1111/j.1365-2125.1993.tb05666.x.

PubMed ID

8448065 [ View in PubMed

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Abstract

1. In microsomes prepared from three human livers, methadone competitively inhibited the O-demethylation of dextromethorphan, a marker substrate for CYP2D6. The apparent Ki value of methadone ranged from 2.5 to 5 microM. 2. Two hundred and fifty-two (252) white Caucasians, including 210 unrelated healthy volunteers and 42 opiate abusers undergoing treatment with methadone were phenotyped using dextromethorphan as the marker drug. Although the frequency of poor metabolizers was similar in both groups, the extensive metabolizers among the opiate abusers tended to have higher O-demethylation metabolic ratios and to excrete less of the dose as dextromethorphan metabolites than control extensive metabolizer subjects. These data suggest inhibition of CYP2D6 by methadone in vivo as well. 3. Because methadone is widely used in the treatment of opiate abuse, inhibition of CYP2D6 activity in these patients might contribute to exaggerated response or unexpected toxicity from drugs that are substrates of this enzyme.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Methadone	Cytochrome P450 2D6	Protein	Humans	No	Substrate Inhibitor	Details