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PubMed · 7389249

Interindividual differences in amitriptyline demethylation.

D E Rollins·G Alván·L Bertilsson·J R Gillette·B Mellström·F Sjöqvist·L Träskman
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Abstract

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.

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Administration, OralAdultAmitriptylineDealkylationHumansHydroxylationIndividualityInjections, IntramuscularMaleMetabolic Clearance RateJournal Article

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D E Rollins, G Alván, L Bertilsson, J R Gillette, B Mellström, F Sjöqvist, L Träskman. 1980. Interindividual differences in amitriptyline demethylation.. https://doi.org/10.1038/clpt.1980.140

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