Imipramine half-life

The metabolism and elimination of TCAs takes several days to occur, the elimination half-life ranging from 20 hours for amitriptyline to 80 hours for protriptyline. The half-life values for the desmethylated metabolites such as desmethylimipramine and nortriptyline are approximately twice those of the parent compounds imipramine and amitriptyline. It is also well established that the half-life values of the TCAs are considerably greater in the elderly, which predisposes such patients to a greater possibility of severe side effects. 

Maprotiline and bupropion cause more seizures than agents such as imipramine, amitriptyline, and nortriptyline. This issue, plus other safety concerns, has significantly limited the use of maprotiline. If maprotiline is used, many clinicians start with a low dose (75 mg per day or less in elderly patients), gradually increasing by 25-mg increments over 2 or more weeks (the drug has a half-life of about 48 hours). Average doses in outpatients are 150 mg, with a maximum of 225 mg. 

Oral contraceptives reduce the clearance of imipramine, probably by reducing hepatic oxidation, and thus increase its half-life. Hydroxylation of amitriptyline is inhibited by contraceptive steroids. The clinical significance is uncertain, but there is at least anecdotal evidence of an increase in antidepressant adverse effects (360). Caution should be exercised when tricyclic antidepressants are used long term in women taking oral contraceptives. 

Half-life. Plasma half-life, imipramine 8 to 20 hours, increased in children, elderly subjects, and after overdose desipramine 10 to 35 hours. 

Preadolescent children demonstrate a shorter half-life of imipramine therefore, several divided doses per day are required. 

Citalopram (9) was about 2-8 times more potent vivo than chlor-imipramine against 5-HT uptake in rat brain or blood platelets but had essentially no effect on uptake of DA or NA.54 In vitro, the two drugs were equlpotent and were competitive inhibitors of 5-HT uptake but about 20-35 times more potent than imipramine or amitriptyline. The citalopram metabolites were also active. In healthy subjects, 9 had a long plasma half-life of 1 to 2 1/2 days.55 Another nitrile, but derived from imipramine,... 

Paroxetine levels might be increased (tricyclic antidepressants (TCAs) inhibit its metabolism) this is evident mainly with amitriptyline, desipramine, imipramine, and nortriptyline. Note that TCA levels could also increase, since paroxetine concomitantly inhibits their metabolism. Studies so far have confirmed this with desipramine and imipramine (whose half-life can increase by 5-fold). 

However when high micromolar concentrations (200 micro M) of 5-HT or of 5-HT uptake inhibitors were used in determining the dissociation half life of H-imipramine, H-paroxetine and H-dtalopram dissociating from human platelet membrane preparations it appears that not only the dissociation half life was prolonged but also that the prolongation was different for each of the three labeled uptake inhibitors [24]. This led to the conclusion that the three labeled ligands each bind to a different domain on the 5-HT transporter. 

Imipramine 150 mg daily has also been reported to enhance some of the hypno-sedative effects of alcohol, and unexplained blackouts lasting a few hours have been described in 3 women after they drank only modest amounts of alcohol they had been taking amitriptyline or imipramine for only a month. The half-life of oral imipramine was about 45% lower in recently detoxified alcoholics (without liver disease) compared with healthy subjects, and the intrinsic clearance was 200% greater. ... 

Two groups of 6 healthy subjects were given a single 100-mg dose of either imipramine or desipramine alone, and then again on day 10 of a 14-day course of ketoconazole 200 mg once daily. It was found that the ketoconazole caused the oral clearance of the imipramine to fall by 17%, its half-life to rise by 15% and the AUC of desipramine, derived from the imipramine, to fall by 9%. No significant changes in the pharmacokinetics of the desipramine were seen. ... 

A single-dose study in healthy subjects found that quinidine 200 mg daily reduced the clearance of imipramine 100 mg by 30% and desipramine 100 mg by 85%. A further study in 2 healthy subjects similarly found that quinidine 50 mg almost doubled the half-life of a single 75-mg dose of trimipramine, which was reflected in some waking EEG changes. ... 

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