Hepatic Metabolism

Hepatic metabolism is the principal method of clearance for the tricyclic and tetracyclic compounds. Only a small portion of drug is eliminated by the kidney. Rates of hepatic metabolism vary widely from person to person, resulting in dramatic differences in steady-state plasma concentrations. Elimination half-lives for most of the tricyclic and tetracyclic compounds average about 24 hours or longer; thus, the drugs can be given once a day (Table 12-2). Amoxapine has a shorter half-life than the other tricyclics and is an exception.

TABLE 12-2. Dosage, clearance, and apparent therapeutic plasma concentrations of tricyclics and tetracyclics

Plasma Therapeutic

Drug Half-life Clearance Dosage range Plasma level



Drug Half-life (hours)

Tertiary tricyclics

Amitriptyline 5-45

Clomipramine 15-60

Doxepin 10-25

Imipramine 5-30

Trimipramine 15-40

Secondary tricyclics

Desipramine 10-30

Nortriptyline 20-55

Protriptyline 55-200 Tetracyclics

Amoxapine 5-10

Maprotiline 25-50

Clearance (L/hour)

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