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    Tramadol undergoes hepatic metabolism via the cytochrome P450 isozyme CYP2B6, CYP2D6 and CYP3A4, being O- and N-demethylated to five different metabolites. Of these, desmetramadol (O-desmethyltramadol) is the most significant since it has 200 times the μ-affinity of (+)-tramadol, and furthermore has an elimination half-life of nine hours, compared with six hours for tramadol itself. As with codeine, in the 6% of the population that have reduced CYP2D6 activity (hence reducing metabolism), there is therefore a reduced analgesic effect. Those with decreased CYP2D6 activity require a dose increase of 30% in order to achieve the same degree of pain relief as those with a normal level of CYP2D6 activity.[85][86]
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    As a result of the metabolism of Ultram in the liver, by CYP 2D6 and CYP 3A4, there are potential drug interactions. Drug interactions are possible with the concomitant administration of Ultram with medications that are CYP 2D6 and CYP 3A4 inhibitors, such as ketoconazole, erythromycin, quinidine, fluoxetine, paroxetine and amitriptyline.
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