Interindividual differences in amitriptyline demethylation.
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.
D000284:Administration, Oral; D000328:Adult; D000639:Amitriptyline / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D003640:Dealkylation; D006801:Humans; D006900:Hydroxylation; D007206:Individuality; D007273:Injections, Intramuscular; D008297:Male; D008657:Metabolic Clearance Rate
D000639:Amitriptyline