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Unit Code 500515:
Imipramine and Desipramine, Serum

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Useful For

Assessing optimal therapeutic levels

 

Assessing potential toxicity

Clinical Information

Imipramine and its metabolite desipramine (Norpramine) are

tricyclic antidepressants used to treat endrogenous depression.

These drugs also have been employed in the treatment of enuresis

in childhood and severe obsessive-compulsive neurosis.

Desipramine has significant stimulatory side effects and is used

when the patient needs a drug with maximal stimulation.

 

Imipramine is administered in doses of 75 mg/day to 150 mg/day in divided

doses. Imipramine has limited bioavailability of approximately 25%

and is 95% protein bound. Imipramine undergoes hepatic metabolism

to desipramine and renal elimination with a clearance of 15 mL/min/kg.

The volume of distribution of imipramine is 23 L/kg and the elimination

half-life is 15 hours to 20 hours.

 

The therapeutic concentration of imipramine and desipramine is

125 ng/mL to 275 ng/mL (sum of both). If desipramine is given, no imipramine

should be detected and the therapeutic concentration for desipramine

alone is 75 ng/mL to 225 ng/mL (see #500516 Desipramine, Plasma). About

1 to 3 weeks of treatment are required before therapeutic effectiveness

becomes apparent.

 

The most frequent untoward reactions are those attributable to

anticholinergic effects: dry mouth, constipation, dizziness, tachycardia,

palpitations, blurred vision, and urinary retention. These side effects

occur at blood concentrations in excess of 300 ng/mL, although they

may occur at therapeutic concentrations in the early state of therapy.

Cardiac toxicity (first-degree heart block) is usually associated with

blood concentrations >500 ng/mL.

 

Concurrent administration of phenothiazines (perphenazine displays

the strongest effect) will cause accumulation of the metabolite as the

conversion of desipramine to 10-hyroxydesipramine is blocked.

Dosage adjustments may be in order in this situation. Desipramine is

metabolized by the cytochrome P450 system; all drugs that activate

the P450 system (ie, phenobarbital) will increase the rate of clearance

of desipramine.

Reference Values

IMIPRAMINE and DESIPRAMINE

      Total therapeutic concentration:  125-275 ng/mL

      Total toxic concentration:  > or =1000 ng/mL

DESIPRAMINE ONLY

      Therapeutic concentration:  75-225 ng/mL

      Toxic concentration: > or =500 ng/mL

Interpretation

Optimal response when imipramine is administered occurs when

the combined total of imipramine and its metabolite desipramine

is in the range of 125 ng/mL to 275 ng/mL.

 

Desipramine, when administered in doses of 100 mg/day to 200 mg/day to

should yield therapeutic levels of 75 ng/mL to 225 ng/mL.

Cautions

No significant cautionary statements.

Clinical Reference

Ziegler VE, Biggs JT, Rosen SH, et al: Imipramine and desipramine

plasma levels: relationship to dosage schedule and sampling time.

J Clin Psychiatry 1978;39:660-663

Key