Metabolism of clomipramine in a Japanese psychiatric population: hydroxylation, desmethylation, and glucuronidation.

We measured the concentrations of clomipramine and its metabolites, N-desmethylclomipramine, 8-hydroxy-N-desmethylclomipramine, 8-hydroxyclomipramine by high-performance liquid chromatography in 108 Japanese psychiatric patients receiving clomipramine hydrochloride PO. The concentrations of the glucuronide conjugates of 8-hydroxyclomipramine and 8-hydroxy-N-desmethylclomipramine were assayed via enzymatic hydrolysis. Although there were large interindividual variations of concentrations of parent, intermediate metabolic compounds, and glucuronide conjugates, significant positive correlations were observed between these drug concentrations and daily doses of clomipramine hydrochloride (mg/kg body weight). Although the metabolic ratios for desmethylation, hydroxylation, and glucuronidation that were calculated from steady-state drug concentrations varied substantially with 36-, 14-, and 28-fold interindividual variations, respectively, apparent poor desmethylators, poor hydroxylators, or poor glucuronidators were not found.