Evidence for a role of cytochrome P450 2D6 and 3A4 in ethylmorphine metabolism.
Article Details
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Liu Z, Mortimer O, Smith CA, Wolf CR, Rane A
Evidence for a role of cytochrome P450 2D6 and 3A4 in ethylmorphine metabolism.
Br J Clin Pharmacol. 1995 Jan;39(1):77-80. doi: 10.1111/j.1365-2125.1995.tb04413.x.
- PubMed ID
- 7756104 [ View in PubMed]
- Abstract
Ethylmorphine is metabolised by N-demethylation (to norethylmorphine) and by O-deethylation (to morphine). The O-deethylation reaction was previously shown in vivo to co-segregate with the O-demethylation of dextromethorphan indicating that ethylmorphine is a substrate of polymorphic cytochrome P450(CYP)2D6. To study further the features of ethylmorphine metabolism we investigated its N-demethylation and O-deethylation in human liver microsomes from eight extensive (EM) and one poor metaboliser (PM) of dextromethorphan. Whereas N-demethylation varied only two-fold there was a 4.3-fold variation in the O-deethylation of ethylmorphine, the lowest rate being observed in the PM. Quinidine, at a concentration of 1 microM, inhibited O-deethylation in microsomes from an EM, but was unable to do so in microsomes from the PM. The immunoidentified CYP2D6 and CYP3A4 correlated with the rates of O-deethylation (r = 0.972) and N-demethylation (r = 0.969), respectively. We conclude that the O-deethylation of ethylmorphine is catalysed by the CYP2D6 in human liver microsomes consistent with previous findings in healthy volunteers.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Ethylmorphine Cytochrome P450 2D6 Protein Humans UnknownSubstrateDetails Ethylmorphine Cytochrome P450 3A4 Protein Humans UnknownSubstrateDetails