[Clinical significance of plasma levels of clomipramine and its desmethylated and hydroxylated metabolites].

Concentrations of clomipramine and its metabolites, N-desmethylclomipramine (DC), 8-hydroxy-N-desmethylclomipramine (HDC) and 8-hydroxyclomipramine (HC), in plasma were determined in 99 patients treated with clomipramine hydrochloride. Doses patients received were not fixed but titrated according to their clinical severity and response to the treatment. Large interindividual variations were present in the concentrations of parent or each metabolic compounds in plasma, however, strong correlations existed between these drug concentrations and daily doses of clomipramine (0.40-5.10 mg/kg of body weight) (r = 0.62-0.80). Metabolic ratios for desmethylation and those for hydroxylation were calculated from these data, and revealed very large inter-individual variations of 30-36 fold and 10-96 fold, respectively. Pharmacological data from 65 of these patients with DSM-III-R mood disorders were analyzed by discriminant analysis using the scores of Global Assessment of Functioning. The overall prediction value for responder or nonresponder was calculated as 70% 2 wk after the initiation of pharmacotherapy. Concentrations of hydroxylated metabolites in plasma does contribute as much to the prediction of clinical response to clomipramine as desmethylated metabolites.