Toxicology. 1997 Feb 14;117(1):13-23.  

Interaction of methadone with substrates of human hepatic cytochrome P450 3A4.

Iribarne C, Dreano Y, Bardou LG, Menez JF, Berthou F.

Equipe d'Accueil EA 948, Laboratoires de Biochimie-Nutrition, Faculte de
medecine, Brest, France.

Methadone, a synthetic drug, is one of the most widely used drugs for opiate
dependency treatment. This drug has been demonstrated to be extensively
metabolized by cytochrome P450 3A4 in human liver microsomes. Thus, the aim of
this in vitro study was to determine if methadone is an inhibitor of other P450s
characterized by their specific catalytic activities. Enzymatic activities
specific to P450 2E1, P450 1A, P450 2B and P450 2C were not inhibited by
methadone. Conversely, nifedipine oxidation, mediated by cytochrome P450 3A4,
was potently inhibited by methadone by a mixed-type inhibition mechanism with a
Ki of 100 microM. Fluvoxamine, a new antidepressant, was shown to be a potent
mixed-type inhibitor of methadone N-demethylation with a Ki of 7 microM.
Finally, methadone appears to be a mixed-type inhibitor and not a suicide
inhibitor of cytochrome P450 3A family. Accordingly, caution should be advised
in the clinical use of methadone when other drugs are administered that are able
to induce or inhibit P450 3A4, such as rifampicin or nifedipine, diazepam and
fluvoxamine.

PMID: 9020195 [PubMed - indexed for MEDLINE]