Enzymes Involved ]
Cytochrome P450 system (CYP-2D6, CYP-3A4, et al.)
CYP-2D6 is also known as debrisoquine 4-hydroxylase.
CYP-2D6 alone is responsible for metabolizing DXM into DXO via a process called O-demethylation.
The other enzymes metabolize DXM into 3-HM and 3-MM. 3-Methoxymorphinan can itself inhibit cytochrome P450-2D6 activity.
The half-life of DXM-Hydrobromide in plasma is about 11 hours.
The hydrobromide salt of DXM is absorbed in the gastrointestinal tract within 30 minutes of ingestion, and all of it may enter the bloodstream. DXM is always metabolized through two pathways, the P450-2D6 and the P450-3A, but it always ends up as 3-hydroxymorphinan (3HM.) When DXM is metabolized by CYP2D6, it turns into DXO first, which is then converted to 3HM by the CYP3A. Most normal individuals, that is, those with no CYP2D6 deficiency, will metabolize roughly 90% of DXM in this way. Occasionaly, and especially when all the P450-2D6 enzymes have been saturated, DXM will be converted to 3-methoxymorphinan by a 3A enzyme first, which is in turnconverted to 3HM by a 2D6 (when one becomes available.)
