Premium
Amitriptyline metabolism: Association with debrisoquin hydroxylation in nonsmokers
Author(s) -
Mellström Britt,
Säwe Juliette,
Bertilsson Leif,
Sjöqvist Folke
Publication year - 1986
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1986.56
Subject(s) - amitriptyline , hydroxylation , demethylation , nortriptyline , chemistry , pharmacology , metabolism , clinical pharmacology , pharmacokinetics , plasma levels , metabolite , endocrinology , medicine , biochemistry , enzyme , gene expression , dna methylation , gene
Eleven healthy nonsmokers with wide variation in the ability to hydroxylate debrisoquin (D) were given single oral doses of amitriptyline and nortriptyline on different occasions. The urinary D/4‐hydroxy‐D ratio correlated significantly (P < 0.01) with all three parameters of amitryptyline disposition measured (total plasma clearance, clearance by demethylation, and clearance by pathways other than demethylation), with r s = − 0.89, − 0.78, and − 0.83, respectively. In contrast, we failed to demonstrate such correlations in a previous sample of smokers. Our data suggest that there may be a common regulation of the hydroxylation of D and the oxidative metabolism of amitriptyline in nonsmokers. It is hypothesized that an additional demethylase/hydroxylase is induced in smokers that is not involved in D hydroxylation. Clinical Pharmacology and Therapeutics (1986) 39, 369–371; doi: 10.1038/clpt.1986.56