Interindividual variations of desmethylation and hydroxylation of amitriptyline in a Japanese psychiatric population

We measured the concentrations in plasma of amitriptyline and its metabolites, nortriptyline and geometric isomers of 10-hydroxynortriptyline and 10-hydroxyamitriptyline, in 73 Japanese psychiatric patients receiving amitriptyline hydrochloride (Tryptanol; Banyu Pharmaceutical Co. Ltd., Tokyo, Japan) by high-performance liquid chromatography. Although there were large interindividual variations of total drug concentrations and concentrations of parent or intermediate metabolic compounds in plasma, significant positive correlations were observed between these drug concentrations and daily doses of amitriptyline hydrochloride (milligrams per kilogram of body weight). The metabolic ratios for both hydroxylation and desmethylation varied substantially with approximately 8- to 19-fold interindividual variations. Frequency distribution histograms and probit analyses of these parameters identified neither definite poor hydroxylators nor poor desmethylators of amitriptyline.