The demethylation of amitriptyline: A cross-over study of steady-state plasma levels of amitriptyline and nortriptyline in depressed patients
Five elderly depressed patients were treated with amitriptyline (AT) and nortriptyline (NT) in turn, in a crossover design. Steady-state plasma drug levels were compared with those calculated for eight healthy subjects of previous single-dose studies. Plasma clearances were on average about 2.5 times lower in the patients than the healthy subjects, but the ratios of the different reaction rates did not differ significantly between the two groups. The interpretation of the ratio of NT levels during AT treatment and NT treatment, in terms of the fraction of AT that is metabolised by demethylation, is discussed. The ratio of NT level to AT level during AT treatment was particularly variable between individuals. This was apparently due to independent variation in (a) the ratio of plasma clearances of AT and NT and (b) the fraction of AT metabolised to NT.