Nonlinear pharmacokinetics of chlorimipramine after infusion and oral administration in patients

In this study the pharmacokinetics of 75 mg and 150 mg chlorimipramine after infusion and tablets was followed for four weeks in chronically treated patients. The clearance was found to be dose dependent. From the time course of the metabolite desmethylchlorimipramine in plasma it can be concluded, that chlorimipramine tablets are resorbed totally. No correlation between pharmacokinetic and improvement parameters could be found. Doubling of the dosage leads to 3 fold chlorimipramine and 4 fold desmethylchlorimipramine concentrations. The estimated half lives are higher than known hitherto. Especially for chronic treatment with 150 mg chlorimipramine, plasma concentration monitoring is recommended, because 20% of the patients did not reach steady state for chlorimipramine and 60% for desmethylchlorimipramine, in these 4 weeks.