Interaction of perphenazine with the kinetics of nortriptyline

The kinetics of nortriptyline in four patients were investigated before and during treatment with perphenazine (24-36 mg/day) by administering 57 mg nortriptyline hydrochloride as an intravenous infusion and evaluating the resulting plasma concentration data according to a two compartment open model. In all patients an increased biological half-life as well as a decreased systemic clearance and rate of metabolism were found in the perphenazine-period, thus confirming the inhibitory effect of perphenazine on the metabolism of nortriptyline found in earlier studies. Some interaction with distribution parameters was also indicated, but on the whole the model parameters did not provide much further information about the interaction. Although the most pronounced changes were found with the patient getting the highest dose of perphenazine, the dose-effect relationship remains obscure.