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 a fter the last dose for determination of clomipramine and desmethylclomipram ine 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 co ncentrations, however, were markedly higher in brain than in serum - 12.5 f old for clomipramine and 7.4 fold for desmethyl clomipramine. The data indi cate that serum and brain concentrations of clomipramine and its demethylat ed metabolite are rapidly exchanged between blood and brain. Assuming that blood and brain kinetics in man and rat are comparable, it is concluded tha t monitoring blood concentrations of clomipramine and desmethylclomipramine is a useful way to evaluate brain concentrations. (C) 2000 Elsevier Scienc e B.V. All rights reserved.