title: Amitriptyline metabolism: association with debrisoquin hydroxylation in nonsmokers.
abstract: 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 less than 0.01) with all three parameters of amitriptyline disposition measured (total plasma clearance, clearance by demethylation, and clearance by pathways other than demethylation), with rs = -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.
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000639:Amitriptyline / Q000097:blood / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D019389:Cytochrome P-450 CYP2D6; D003647:Debrisoquin / Q000031:analogs & derivatives / Q000378:metabolism / Q000652:urine; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006900:Hydroxylation; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009661:Nortriptyline / Q000097:blood / Q000378:metabolism*; D010641:Phenotype
chemical_list: D000639:Amitriptyline; C012359:4-hydroxydebrisoquin; D009661:Nortriptyline; D006899:Mixed Function Oxygenases; D019389:Cytochrome P-450 CYP2D6; D003647:Debrisoquin