Is O-Desmethyltramadol an inducer of cyp2d6?

[FnX]

Or why does the presence of it in the bloodstream lead to increased tramadol -> O-Desmethyltramadol conversion rate and staggered doses producing more analgesia? Similar 'ceiling effect' as codeine to morphine conversion? Though the metabolism and metabolic pathways of tramadol are studied quite extensively, there doesn't seem to be much research done on individual metabolites of tramadol, so I'm having a hard time finding the answers I'm looking for.

 

[Kittycat5]

I do not believe o-desmethyltramadol is a substrate or inducer of CYP2D6. It can be converted to the M5 metabolite (N,O didesmethyltramadol) via CYP 3A4 and 2BG or conjugated to the glucuronide via UGT enzymes but 2D6 doesnt have much if any involvement.

The staggered dose producing greater analgesia is not something that may be correct. The tmax is longer and cmax and AUC lower of M1 (o-Desmethyltramadol) after single doses of immediate release tramadol compared to SR version or multiple daily dosing. Furthermore, the clearance of tramadol and its metabolites is stereoselective. The enantiomers are cleared at different rates. (+) tramadol and (-)M1 are eliminated slower than (-) tramadol and (+) M1. (+) M1 is probably the most potent analgesic of any metabolite or enantiomer of tramadol or its metabolites, so faster clearance, and thus lower plasma levels of (+) M1 would result in less analgesia until you hit steady state.