Amitriptyline excretion

Pittard WB 3rd, O Neal W Jr. Amitriptyline excretion in human milk. J Clin Psychopharmacol 1986 6(6) 383 1. 

Pregnancy Category D- amitriptyline, imipramine, nortriptyline Category C -amoxapine, clomipramine, desipramine, doxepin, protriptyline, trimipramine). Lactation These agents are excreted into breast milk in low concentrations. 

Brixen-Rasmussen L, Halgrener J, j0rgensen A. Amitriptyline and nortriptyline excretion in human breast milk. Psychopharmacology 1982 76 94—5. 

There are few reports on the excretion of antidepressant drugs in breast milk, even though postpartum depression is relatively common. In a 32-year-old woman who took imi-pramine 200 mg/day from 1 month postpartum imipramine and desipramine were detectable in breast milk (135). There have also been reports that amitriptyline (136), desipramine (137), and nortriptyline (138,139) were detectable in the milk of nursing mothers and in the plasma of the mothers and infants. Neither parent compound nor metabolite were detected in infants serum, except for two infants who had low concentrations of 10-hydroxynortriptyline. There were no adverse effects in any of the infants. The use of antidepressants during lactation has been reviewed, including 15 studies in which serum concentrations of antidepressants were obtained from nursing infants (140). 

When a dmg is in its unionised form it will more readily diffuse from the urine to the blood. In an acidic urine, acidic drugs will diffuse back into the blood from the urine. Acidic compounds such as nitrofurantoin are excreted faster when the urinary pH is alkaline. Amfetamine, imipramine and amitriptyline are excreted more rapidly in acidic urine. The control of urinary pH in studies of pharmacokinetics is thus vital. It is difficult, however, to find compounds to use by the oral route for deliberate adjustment of urinary pH. Sodium bicarbonate and ammonium chloride may be used but are unpalatable. Intravenous administration of acidifying salt solutions presents one approach, especially for the forced diuresis of basic dmgs in cases of poisoning. 

Nortriptyline is a secondary amine dibenzocycloheptene TCA (Fig. 21.8) as well as the major metabolite of amitriptyline. Similar to desipramine, nortriptyline appears in mother s milk and is metabolized by CYP2D6 to the primary amine and by ring hydroxylation to its E-10-hydroxy metabolite (Table 21.2). Approximately one-third of a dose of nortriptyline is excreted in urine as metabolites within 24 hours, and small amounts are excreted in feces via biliary elimination. 

Vitamin C 1 g three times daily was found to have no effect on the urinary excretion of methotrexate 45 mg given intravenously to a woman with breast cancer, despite the urine becoming more acidic at pH 5.9 (compare Methotrexate + Urinary alkalinisers , p.654). She was also receiving oral cyclophosphamide, propranolol, amitriptyline, perphenazine and prochlorperazine. No special precautions appear to be necessary. 

When, on the other hand, the groups are divided according to "high or low MHPG values (discrimination value 0.9 mg/24 h), or according to whether they were responders or non-responders, it could be seen that amitriptyline causes variable but definite changes in excretion in some of these (Fig 2). 

FIG. 2. MHPG excretion before and after treatment with amitriptyline. 

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