Steady state concentrations of clomipramine and its major metabolite desmethylclomipramine in rat brain and serum after oral administration of clomipramine.

Twenty male Sprague-Dawley rats received five oral doses of clomipramine 20 mg/kg at 4-h intervals. The animals were decapitated 1, 2, 3, 5 and 12 h after the last dose for determination of clomipramine and desmethylclomipramine in serum and frontal cerebral cortex. Time dependent concentrations of clomipramine and desmethylclomipramine paralleled in serum and brain. Half-lives were similar in serum and brain with 7.8 versus 6.2 h and 5.5 versus 5.0 h for clomipramine and desmethylclomipramine, respectively. Absolute concentrations, however, were markedly higher in brain than in serum - 12.5 fold for clomipramine and 7.4 fold for desmethylclomipramine. The data indicate that serum and brain concentrations of clomipramine and its demethylated metabolite are rapidly exchanged between blood and brain. Assuming that blood and brain kinetics in man and rat are comparable, it is concluded that monitoring blood concentrations of clomipramine and desmethylclomipramine is a useful way to evaluate brain concentrations.