Pharmacokinetic aspects on once-daily nortriptyline administration

Steady state nortriptyline plasma levels have been studied in 21 endogenously depressed patients treated with a single 150-mg morning dose and compared to theoretical curves, calculated from previously known kinetic data. Fairly good agreement between predicted and experimentally found concentrations was observed. The fluctuation between maximal and minimal drug levels within the dosage interval was found to be more pronounced than with a t.i.d. dosage regimen, but still limited (mean ratio = 1.54; range = 1.0--2.16), and the minimum levels (mean = 102 ng/ml; range 46--250 ng/ml) were well compatible with published t.i.d. data. The biological half-life (mean = 39 h; range 24--86 h) agreed well with previously published data for volunteers. It is concluded that once-daily administration of nortriptyline results in relatively flat concentration curves as one would expect from the kinetic features of the drug. The clinical outcome is discussed in a separate paper.