Hydrocodone Metabolism


Hydrocodone is associated with the following name brands:

            Hycodan, Norco, Vicodin, Cogesic, Lortab, Lorcet, Hycet, Anexia, Zydone, Vicoprofen


Hydrocodone is metabolized by several routes. It is O-demethylated (CYP2D6 enzyme) to form hydromorphone and is N-demethylated (CYP 3A4) to form norhydrocodone. Hydrocodone is also reduced to form hydrocodol, also known as dihydrocodeine. All three metabolites are psychoactive and hydromorphone has greater activity than the parent drug. The detection of any of the following compounds in a patient’s urine sample is consistent with hydrocodone use:  hydrocodone, norhydrocodone, hydromorphone and dihydrocodeine. 


In a controlled study where individuals were given a single 20 mg dose of hydrocodone, peak urinary concentrations of hydrocodone and metabolites were detected 3-9 hours after use. The relative concentrations were norhydrocodone > hydrocodone > hydromorphone > dihydrocodeine. At a 50 ng/mL cutoff, detection times were 28 hours for hydrocodone, 40 hours for norhydrocodone, 26 hours for hydromorphone and 16 hours for dihydrocodeine. (Cone et al, J Anal Tox 2013; 37: 486-494) 


The relative urinary concentrations of hydrocodone and metabolites may vary according to sex, age and use of CYP2D6 and CYP 3A4 inhibitors such as antifungal agents or selective serotonin reuptake inhibitors. (Barakat et al, J Anal Tox 2014; 38: 404-409)