Linear Kinetics

Most of the tricyclics have linear kinetics; that is, concentration increases in proportion to dose within the therapeutic range. There are exceptions. Desipramine, for example, appears to have nonlinear kinetics in the usual dose range (Nelson and Jatlow 1987). Rapid metabolizers of desipramine are most likely to display nonlinear changes during the time when the dose is increasing. In these patients, a disproportionate rise in the drug concentration occurs when the dose is increased. In cases of overdose, nonlinear changes are more likely to occur, and the clinician cannot assume that usual rates of drug elimination will be maintained.

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