Abstract

The urinary excretion of amitriptyline (AMT) and seven of its metabolites was studied by mass spectrometry in 10 depressive in-patients treated to steady-state condition with oral amitriptyline. An average of 68.3% of the dose was recovered in the urine, of which 68.6% was present as conjugates. Hydroxynortriptyline and its conjugate represented 54% of the total recovery. There was marked variation in metabolite pattern between patients. The variations were not due to concomitant medication with benzodiazepines. There was no correlation between the plasma and urine concentrations of AMT and its metabolites, except for amitriptyline conjugates. Two groups of patients could be distinguished - low and high excretors, who displayed alternative routes of metabolism. The disappearance rate of AMT from plasma was determined by the metabolic clearance of AMT to its metabolites. It varied considerably between patients.

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