Methadone is used to treat moderate to severe
pain in patients not responsive to
non-narcotic analgesics and for maintenance treatment of
opioid addiction.
Methadone is primarily metabolized by N-demethylation to an inactive metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidene (EDDP) by
CYP3A4 and
CYP2B6. Establishing expected concentrations for metabolism of
methadone to EDDP using urine excretion data may be useful for monitoring "medications" and toxicity. Urine specimens from
chronic pain patients were collected during routine
clinic visits.
Methadone and EDDP were quantified by liquid chromatography-tandem mass spectrometry. Approximately 8,000 subjects who reported taking
methadone had
creatinine concentrations ≥20 mg/dL, and excreted concentrations of
methadone and EDDP above ≥100 ng/mL were selected. The median
methadone urine concentration was 3.03 mg/g cr. Ninety-five percent of the population had concentrations between 0.175 and 20.9 mg/g cr. EDDP was, on average, twice the
methadone concentration. The wide variance in relationship of
methadone to its metabolite was not concentration-dependent. Variability between subjects was larger than variability within subjects. As the urinary pH increased, the proportion of excreted EDDP increased, implying a preferred excretion of EDDP.