Interindividual differences in amitriptyline demethylation

Clin Pharmacol Ther. 1980 Jul;28(1):121-9. doi: 10.1038/clpt.1980.140.


Amitriptyline (AT) and its demethyl metabolite nortriptyline (NT) were given orally and intramuscularly to 6 normal subjects, and the areas under the blood concentration--time curves (AUC) were calculated. The mean unbound fraction of AT and NT in plasma was 5.4% and 8.3%, respectively. The blood-plasma ratio of NT was nearly double that of AT, which was close to unity. The mean systemic availability of oral relative to intramuscular AT and NT was 43% and 61%. The calculated mean oral blood clearance of AT as measured by dose (oral)/AUC was 1.6 1/min. The demethylation of orally administered AT varied considerably between the 6 individuals (from 25% to 89%) and correlated with oral drug clearance. Demethylation was estimated from the AUC applied to the NT metabolite. The estimated oral clearance of AT from demethylation ranged from 0.21 to 1.80 1/min.

MeSH terms

  • Administration, Oral
  • Adult
  • Amitriptyline / administration & dosage
  • Amitriptyline / blood
  • Amitriptyline / metabolism*
  • Dealkylation
  • Humans
  • Hydroxylation
  • Individuality
  • Injections, Intramuscular
  • Male
  • Metabolic Clearance Rate


  • Amitriptyline