The kinetics of amitriptyline following single oral dose administration to man

Amitriptyline and its metabolite, nortriptyline, were measured in the plasma of eight humans for 96 hours following oral administration of a 75 mg dose of amitriptyline hydrochloride. Based on the 8 to 96 hour post dosing plasma concentration data, the terminal exponential half life of amitriptyline ± S.D. was 22.4±4.3 hr. Based on the 24 to 96 hour concentration data, the 'apparent' terminal half time of nortriptyline ± S.D. was 26.0±7.4 hours for seven subjects. For these same seven subjects the relative area under the plasma concentration time curve of nortriptyline ± S.D. was only 0.88±0.34 times that of amitriptyline. One subject whose apparent nortriptyline half time was 108 hours had a nortriptyline bioavailability 3.83 times that of amitriptyline. Average steady state plasma levels for 12 psychiatric patients who had received a 50 mg oral dose of amitriptyline three times a day for an average of 32 days could be predicted from the single dose plasma clearance of amitriptyline.