Single-dose prediction of amitriptyline and nortriptyline requirement in unipolar depression

Eleven adult patients received a single 100-mg dose of amitriptyline or nortriptyline for pharmacokinetic assessment prior to being placed on a regular dosage of the same drug to achieve steady-state concentrations. Drug plasma levels were determined by a gas chromatographic electron capture detector procedure. For both amitriptyline and nortriptyline there was a high correlation between the plasma concentration measured 18 to 42 hours after the single dose and the steady-state concentration. One half of the steady state variability was accounted for by the single-dose drug level determination. A simple formula was devised using the blood level obtained after a test dose to predict the dosage necessary to obtain a desired steady-state concentration. The data suggest that this approach may have practical clinical value in initiating treatment with tricyclic antidepressants.