Nortriptyline in depressed patients with high plasma levels. II

Eighteen depressed patients were routinely treated with 100 mg nonriptyline nightly for 4 wk. Steady‐state plasma nortriptyline concentrations were measured at weekly intervals for each patient at the same time as clinical assessments were carried out. Steady‐state nonriptyline levels ranged between 120 µg/L and 681 µg/L (mean, 293 µg/L), which represents a 6‐fold interindividual variation. A single oral dose of 100 mg nonriptyline was given to 17 of the 18 patients prior to treatment. Plasma nortriptyline concentrations were obtained at regular intervals over a 3‐day period. Several kinetic parameters were calculated for each patient. The plasma nonriptyline half‐life (t ½ ) ranged from 22 to 88 hr and the plasma clearance ranged between 8 and 55 L/hr. Highly significant correlations were obtained between steady‐state nortriptyline levels and both t ½ (p < 0.01) and clearance (p < 0.0001). A high correlation (p < 0.0001) was also obtained between single‐dose 48‐hr nonriptyline levels and steady‐state nonriptyline levels. We have been able to demonstrate a strong relationship between individual patient differences in nonriptyline kinetics and steady‐state plasma concentrations and associated therapeutic effects. The pharmacokinetic data obtained in the patients appear to be different to those reponed in studies carried out in normal healthy volunteers. Reasons for this are discussed. The use of simple kinetic parameters in predicting the high nonriptyline levels is also discussed.