Plasma steady-state concentrations of hydroxylated metabolites of clomipramine

Plasma clomipramine, desmethylclomipramine, 8-hydroxyclomipramine, and 8-hydroxydesmethylclomipramine concentrations were measured in nine obsessive-compulsive outpatients. The mean dose of clomipramine at steady state was 237.5 +/- 51.8 (SD) mg/24 hr. The mean concentrations at steady state were: clomipramine, 147.5 +/- 57.5; desmethylclomipramine, 313.0 +/- 170.0; 8-hydroxyclomipramine, 56.1 +/- 20.9; and 8-hydroxydesmethylclomipramine, 152.7 +/- 83.2 ng/ml. In vitro, the hydroxymetabolites of clomipramine and desmethylclomipramine exhibited serotonin reuptake potency of the same order as that of the parent compounds.