Pharmacokinetic studies in obsessional patients.

As part of a larger controlled study, 9 patients with chronic obsessive-compulsive rituals received oral clomipramine (Anafranil, Geigy Pharmaceuticals) and behavioural treatment. Dosage was 20 mg clomipramine during the first three days of treatment, increasing gradually over the next few weeks to a maximum daily dose of 200 mg clomipramine unless side-effects dictated a lower dose. Blood was sampled at weekly intervals and the plasma fraction analyzed simultaneously for clomipramine and its primary metabolic breakdown product, N-desmethylclomipramine, using a double radioisotope derivative technique. Plasma concentrations of clomipramine and desmethylclomipramine were observed to rise as the administered dose was increased during the first few weeks of treatment. However, within seven to fourteen days of constant daily dosing steady-state levels were reached in the plasma of clomipramine and its metabolite. Higher plasma levels were found with higher doses. Steady plasma clomipramine levels appeared to be related to dosage, the mean steady-state plasma concentrations between weeks 5 and 11 of treatment being 99 ng/ml, 145 ng/ml and 180 ng/ml, in patients receiving daily doses of 100, 150 and 200 mg clomipramine, respectively. In contrast, plasma metabolite levels did not show any apparent relationship to dosage. In most patients, the concentration of desmethylchlomipramine in the plasma was approximately twice that of the parent compound.