The TCA drugs are well absorbed from the gastrointestinal tract, are extremely lipid soluble, and bind extensively to plasma proteins. Their half-lives range from 8 to 89 hours (Table 33.1). Several days to weeks are required both to achieve steady-state serum levels and for complete elimination of these agents from the body. Long half-lives make most of these agents amenable to dosing once a day, generally at bedtime.

Drug inactivation generally occurs through oxidative metabolism by hepatic microsomal enzymes. Tertiary amines are converted to secondary amines, which generally possess biological activity and are frequently in serum at levels equal to or greater than that of the parent tertiary amine. A second route of inacti-vation includes conjugation of hydroxylated metabolites with glucuronic acid.

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